Chlamydia antigens

ABSTRACT

The invention provides  Chlamydia  antigens for use in the treatment, prevention and/or diagnosis of  Chlamydia  infection. In particular, the invention provides antigens CT733, CT153, CT601, CT279, CT443, CT372, CT456, CT381, CT255, CT341, CT716, CT745, CT387, CT812, CT869, CT166, CT175, CT163, CT214, CT721, CT127, CT043, CT823 and/or CT600 from  C. trachomatis  for the treatment, prevention or diagnosis of  Chlamydia  infection.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. Ser. No. 14/035,750, filedSep. 24, 2013, which is a continuation of U.S. Ser. No. 13/255,002,filed Nov. 21, 2011, now U.S. Pat. No. 8,568,732, which is a §371 filingof PCT/IB2010/050988, filed Mar. 8, 2010, and claims the benefit of U.S.provisional application 61/157,921, filed Mar. 6, 2009, from whichapplications priority is claimed pursuant to 35 U.S.C. §§119/120, andwhich applications are incorporated herein by reference in theirentireties.

TECHNICAL FIELD

This invention is in the field of Chlamydia trachomatis proteins andtheir uses.

BACKGROUND ART

Vaccine development has been identified as essential to controllinginfection with C. trachomatis. Vaccines against C. trachomatis appear toelicit protective T-cell and/or B-cell immunity in the genital tractmucosa.

Protective immunity to C. trachomatis seems to depend on a Th1-polarizedcell-mediated immune response, in particular on CD4+ lymphocytessecreting IFNγ. For example, depletion of CD4+ T cells in mice resultsin loss of protective immunity, and adoptive transfer ofChlamydia-specific CD4+ T cells confers protection against challengewith C. trachomatis. Furthermore, recent studies report that C.trachomatis infection in mice induces a CD4-Th1 protective immuneresponse, indicating that critical Chlamydia antigens are processed andpresented via the MHC class II pathway (Brunham R C and Rey-Ladino J(2005), Nat Rev Immunol 5: 149-1611; Su H and Caldwell H D (1995),Infect Immun 63: 3302-3308).

Although B-cells and antibodies do not have a decisive role inresolution of primary infection, they are likely to be important forenhancing the protective effector T-cell response and to be required tocontrol re-infection with various mechanisms such as antibody-mediatedneutralization and opsonization.

Because immune protection against infection with C. trachomatis islikely to be mediated by immunization with C. trachomatis proteins thatare targets of CD4+ T cells and that are capable of inducing B-cellresponses, identification of such proteins is particularly important. Itis therefore an object of the invention to provide further antigens foruse in Chlamydia vaccines.

DISCLOSURE OF THE INVENTION

The invention identifies Chlamydia antigens for use in the treatment,prevention and/or diagnosis of Chlamydia infection. In particular, theinvention provides one or more of the following antigens (e.g. 1, 2, 3,4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22,23, 24, 25, 26, 27, 28, 29 or 30) from C. trachomatis for the treatment,prevention or diagnosis of Chlamydia infection (and, in particular, C.trachomatis infection): CT733, CT153, CT601, CT279, CT443, CT372, CT456,CT381, CT255, CT341, CT716, CT745, CT812, CT869, CT387, CT166, CT175,CT163, CT214, CT721, CT127, CT043, CT823, CT600, CT711, CT114, CT480,CT089, CT734 and CT016 for example, one or more of CT733, CT153, CT601,CT279, CT443, CT372, CT456, CT381, CT255, CT341, CT716 and CT745.Inparticular, the invention provides proteins for use in the treatment,prevention and/or diagnosis of Chlamydia infection (and, in particular,C. trachomatis infection). Immunisation with the proteins is preferablyable to induce a specific CD4+ Th1 cell mediated response againstChlamydia.

In one embodiment, the nucleic acid sequence and/or amino acid sequenceof the protein comprises the sequence presented in SEQ ID NO:1 and SEQID NO:2 respectively. This protein is also known as “CT733” and isannotated as a hypothetical protein from C. trachomatis. In anotherembodiment, the nucleic acid sequence and/or amino acid sequence of theprotein comprises the sequence presented in SEQ ID NO:3 and SEQ ID NO:4respectively. This protein is also known as “CT153” and is annotated asMACPF/membrane-attack complex (MAC)/perforin from C. trachomatis. Inanother embodiment, the nucleic acid sequence and/or amino acid sequenceof the protein comprises the sequence presented in SEQ ID NO:5 and SEQID NO:6 respectively. This protein is also known as “CT601” from C.trachomatis. In another embodiment, the nucleic acid sequence and/oramino acid sequence of the protein comprises the sequence presented inSEQ ID NO:7 and SEQ ID NO:8 respectively. This protein is also known as“CT279” from C. trachomatis. In another embodiment, the nucleic acidsequence and/or amino acid sequence of the protein comprises thesequence presented in SEQ ID NO:9 and SEQ ID NO:10 respectively. Thisprotein is also known as “CT443” from C. trachomatis. In anotherembodiment, the nucleic acid sequence and/or amino acid sequence of theprotein comprises the sequence presented in SEQ ID NO:1 1 and SEQ IDNO:12 respectively. This protein is also known as “CT372” from C.trachomatis. In another embodiment, the nucleic acid sequence and/oramino acid sequence of the protein comprises the sequence presented inSEQ ID NO:13 and SEQ ID NO:14 respectively. This protein is also knownas “CT456” from C. trachomatis. In another embodiment, the nucleic acidsequence and/or amino acid sequence of the protein comprises thesequence presented in SEQ ID NO:15 and SEQ ID NO:16 respectively. Thisprotein is also known as “CT381” from C. trachomatis. In anotherembodiment, the nucleic acid sequence and/or amino acid sequence of theprotein comprises the sequence presented in SEQ ID NO:39 and SEQ IDNO:40 respectively. This protein is also known as “CT255” from C.trachomatis. In another embodiment, the nucleic acid sequence and/oramino acid sequence of the protein comprises the sequence presented inSEQ ID NO:41 and SEQ ID NO:42 respectively. This protein is also knownas “CT341” from C. trachomatis. In another embodiment, the nucleic acidsequence and/or amino acid sequence of the protein comprises thesequence presented in SEQ ID NO:43 and SEQ ID NO:44 respectively. Thisprotein is also known as “CT716” from C. trachomatis. In anotherembodiment, the nucleic acid sequence and/or amino acid sequence of theprotein comprises the sequence presented in SEQ ID NO:45 and SEQ IDNO:46 respectively. This protein is also known as “CT745” from C.trachomatis. In another embodiment, the nucleic acid sequence and/oramino acid sequence of the protein comprises the sequence presented inSEQ ID NO:47 and SEQ ID NO:48, respectively. This protein is also knownas “CT387” from C. trachomatis and is annotated as a hypotheticalprotein. In another embodiment, the nucleic acid and/or amino acidsequence of the protein comprises the sequence presented in SEQ ID NO:49and SEQ ID NO:50, respectively. This protein is also known as “CT812”from C. trachomatis and is annotated as a polymorphic outer membraneprotein. In another embodiment, the nucleic acid and/or amino acidsequence of the protein comprises the sequence presented in SEQ ID NO:51and SEQ ID NO:52, respectively. This protein is also known as “CT869”from C. trachomatis and is annotated as a polymorphic outer membraneprotein. In another embodiment, the nucleic acid and/or amino acidsequence of the protein comprises the sequence presented in SEQ ID NO:53and SEQ ID NO:54, respectively. This protein is also known as “CT166”from C. trachomatis. In another embodiment, the nucleic acid and/oramino acid sequence of the protein comprises the sequence presented inSEQ ID NO:55 and SEQ ID NO:56, respectively. This protein is also knownas “CT175” from C. trachomatis. In another embodiment, the nucleic acidand/or amino acid sequence of the protein comprises the sequencepresented in SEQ ID NO:155 and SEQ ID NO:156, respectively. This proteinis also known as “CT163” from C. trachomatis. In another embodiment, thenucleic acid and/or amino acid sequence of the protein comprises thesequence presented in SEQ ID NO:159 and SEQ ID NO:160, respectively.This protein is also known as “CT214” from C. trachomatis. In anotherembodiment, the nucleic acid and/or amino acid sequence of the proteincomprises the sequence presented in SEQ ID NO:163 and SEQ ID NO:164,respectively. This protein is also known as “CT721” from C. trachomatis.In another embodiment, the nucleic acid and/or amino acid sequence ofthe protein comprises the sequence presented in SEQ ID NO:167 and SEQ IDNO:168, respectively. This protein is also known as “CT127” from C.trachomatis.

In some embodiments, the protein is a variant of a protein as describedabove. For example, the protein may comprise one or more mutations (forexample, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more mutations) in thesequence of SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 19, 20, 21, 22,23, 24, 40, 42, 44, 46, 48, 50, 52, 54, 56, 136, 140, 156, 160, 164 or168, for example, in the sequence of SEQ ID NO: 2, 4, 6, 8, 10, 12, 14,16, 40, 42, 44, or 46. Preferred mutations are those which do not causea significant conformational change in the protein such that the proteinof the invention retains the ability to elicit an immune responseagainst the wild-type Chlamydia protein. The proteins having thesequences presented in SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 40, 42,44, 46, 48, 50, 52, 54 and 56 are the wild-type proteins.

In some embodiments, the one or more mutations are present in theN-terminal portion of the protein, for example, between residues 1 and20 of the protein, between residues 21 and 40, between residues 41 and60, between residues 1 and 60 or between residues 1 and 40 of theprotein. In some embodiments, the one or more mutations are present inthe C-terminal portion of the protein, for example, between theC-terminal 20 residues of the protein, between residues 21 and 40 fromthe C-terminus, between residues 41 and 60 from the C-terminus; betweenresidues 1 and 60 from the C-terminus or between residues 1 and 40 fromthe C-terminus of the protein.

Preferably, the amino acid sequences contain fewer than twenty mutations(e.g. 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or1). Each mutation preferably involves a single amino acid and ispreferably a point mutation. The mutations may each independently be asubstitution, an insertion or a deletion. Preferred mutations are singleamino acid substitutions. The proteins may also include one or more(e.g. 1, 2, 3, 4, 5, 6, 7, 8, 9, etc.) single amino acid deletionsrelative to the Chlamydia sequences. The proteins may also include oneor more (e.g. 1, 2, 3, 4, 5, 6, 7, 8, 9, etc.) insertions (e.g. each of1, 2, 3, 4 or 5 or more amino acids) relative to the Chlamydiasequences. Deletions, substitutions or insertions may be at theN-terminus and/or C-terminus, or may be between the two termini. Thus atruncation is an example of a deletion. Truncations may involve deletionof up to 40 (or more) amino acids at the N-terminus and/or C-terminus(for example, 1-10, 11-40, 41-70, 71-100 or more amino acids).

Amino acid substitutions may be to any one of the other nineteennaturally occurring amino acids. Preferably, a substitution mutation isa conservative substitution. Alternatively, a substitution mutation is anon-conservative substitution. A conservative substitution is commonlydefined as a substitution introducing an amino acid having sufficientlysimilar chemical properties, e.g. having a related side chain (e.g. abasic, positively charged amino acid should be replaced by anotherbasic, positively charged amino acid), in order to preserve thestructure and the biological function of the molecule.Genetically-encoded amino acids are generally divided into fourfamilies: (1) acidic i.e. aspartate, glutamate; (2) basic i.e. lysine,arginine, histidine; (3) non-polar i.e. alanine, valine, leucine,isoleucine, proline, phenylalanine, methionine, tryptophan; and (4)uncharged polar i.e. glycine, asparagine, glutamine, cysteine, serine,threonine, tyrosine. Phenylalanine, tryptophan, and tyrosine aresometimes classified jointly as aromatic amino acids. In general,substitution of single amino acids within these families does not have amajor effect on the biological activity. Further examples ofconversative substitutions that may be used in the invention arepresented in Table 1.

TABLE 1 More Preferred Amino Acid Synonymous Groups Synonymous GroupsSer Gly, Ala, Ser, Thr, Pro Thr, Ser Arg Asn, Lys, Gln, Arg, His Arg,Lys, His Leu Phe, Ile, Val, Leu, Met Ile, Val, Leu, Met Pro Gly, Ala,Ser, Thr, Pro Pro Thr Gly, Ala, Ser, Thr, Pro Thr, Ser Ala Gly, Thr,Pro, Ala, Ser Gly, Ala Val Met, Phe, Ile, Leu, Val Met, Ile, Val, LeuGly Ala, Thr, Pro, Ser, Gly Gly, Ala Ile Phe, Ile, Val, Leu, Met Ile,Val, Leu, Met Phe Trp, Phe, Tyr Tyr, Phe Tyr Trp, Phe, Tyr Phe, Tyr CysSer, Thr, Cys Cys His Asn, Lys, Gln, Arg, His Arg, Lys, His Gln Glu,Asn, Asp, Gln Asn, Gln Asn Glu, Asn, Asp, Gln Asn, Gln Lys Asn, Lys,Gln, Arg, His Arg, Lys, His Asp Glu, Asn, Asp, Gln Asp, Glu Glu Glu,Asn, Asp, Gln Asp, Glu Met Phe, Ile, Val, Leu, Met Ile, Val, Leu, MetTrp Trp, Phe, Tyr Trp

Examples of non-conservative substitutions that may be used in theinvention include the substitution of an uncharged polar amino acid witha nonpolar amino acid, the substitution of a nonpolar amino acid with anuncharged polar amino acid, the substitution of an acidic amino acidwith a basic amino acid and the substitution of a basic amino acid withan acidic amino acid.

Mutations may also be introduced to improve stability, e.g., theinsertion of disulphide bonds (van den Akker et al. Protein Sci., 1997,6:2644-2649). For example, the protein may comprise an amino acidsequence having sequence identity to the amino acid sequence of any oneof SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 19, 20, 21, 22, 23, 24,40, 42, 44, 46, 48, 50, 52, 54, 56, 136, 140, 156, 160, 164 and 168, forexample, of any one of SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 40, 42,44 and 46. The degree of sequence identity is preferably greater than50% (e.g. 60%, 70%, 80%, 90%, 95%, 97%, 98%, 99% or more). Theseproteins include homologs, orthologs, allelic variants and functionalmutants. Identity between proteins is preferably determined by theSmith-Waterman homology search algorithm as implemented in the MPSRCHprogram (Oxford Molecular), using an affine gap search with parametersgap open penalty=12 and gap extension penalty=1.

The Chlamydia protein of the invention may comprise one or more aminoacid derivatives. By “amino acid derivative” is intended an amino acidor amino acid-like chemical entity other than one of the 20 geneticallyencoded naturally occurring amino acids. In particular, the amino acidderivative may contain substituted or non-substituted, linear, branched,or cyclic alkyl moieties, and may include one or more heteroatoms. Theamino acid derivatives can be made de novo or obtained from commercialsources (Calbiochem-Novabiochem AG; Sachem).

In some embodiments, the variant protein is a homologous protein from C.pneumoniae, C. psittaci, C. pecorum, C. muridarum or C. suis.

The invention further provides a protein comprising or consisting of afragment of a protein comprising or consisting of the amino acidsequence of any of SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 19, 20,21, 22, 23, 24, 40, 42, 44, 46, 48, 50, 52, 54, 56, 136, 140, 156, 160,164 or 168, for example, of any one of SEQ ID NO: 2, 4, 6, 8, 10, 12,14, 16, 40, 42, 44 or 46, or a fragment of a variant thereof. Thefragment should comprise at least n consecutive amino acids from theprotein and, depending on the particular sequence, n is 6 or more (e.g.8, 11, 16, 31, 51, 76, 121, 181, 231, 281, 331, 381, 431, 440, 445, 446,481, 531, 581, 631, 681, 731, 781, 801, 806, 808 or more). The fragmentis n-1 amino acids or less in length, wherein n=the number of aminoacids in the full length protein (e.g. n-5, n-20, n-50, n-110, n-180,n-240, n-310, n-380, n-445, n-515, n-595, n-675, n-745, n-785, n-800amino acids or less in length). Preferably the fragment comprises one ormore epitopes from the protein. Preferably, one or more of the epitopesis an MHC class II epitope, for example, a CD4+ T cell epitope. In someembodiments, the fragment comprises or consists of the amino acidsequence of any of SEQ ID NOs 64, 66, 68, 70, 72, 74, 76, 78, 80, 82,84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114,116, 118, 120, 122, 124, 126, 128, 130, 132, 134, 138, 142, 146, 150,154, 158, 162, 166 and 170. In some embodiments, the invention providesa protein comprising or consisting of a fragment of a protein comprisingor consisting of the amino acid sequence recited in SEQ ID NO: 122.Table 3 below shows which fragments correspond to which full lengthsequences.

TABLE 3 SEQ ID NO. for Annotation full length sequence SEQ ID NO. forfragment CT733 1 63 CT733 2 64 CT153 3 65 CT153 4 66 CT601 5 67 CT601 668 CT279 7 69 CT279 8 70 CT443 9 71 CT443 10 72 CT372 11 73 CT372 12 74CT456 13 75 CT456 14 76 CT381 15 77 CT381 16 78 CT043 17 79 CT043 18 80CT711 19 81 (nucleotide); 82 (protein) CT114 20 83 (nucleotide); 84(protein) CT480 21 85 (nucleotide); 86 (protein) CT089 22 87(nucleotide); 88 (protein) CT734 23 89 (nucleotide); 90 (protein) CT01624 91 (nucleotide); 92 (protein) TC0551 (CT279) 25 93 TC0551 (CT279) 2694 TC0651 (CT372) 27 95 TC0651 (CT372) 28 96 TC0727 (CT443) 29 97 TC0727(CT443) 30 98 TC0313 (CT043) 31 99 TC0313 (CT043) 32 100 TC0890 (CT601)33 101 TC0890 (CT601) 34 102 TC0741 (CT456) 35 103 TC0741 (CT456) 36 104TC0660 (CT381) 37 105 TC0660 (CT381) 38 106 CT255 39 107 CT255 40 108CT341 41 109 CT341 42 110 CT716 43 111 CT716 44 112 CT745 45 113 CT74546 114 CT387 47 115 CT387 48 116 CT812 49 117 (mature full length); 119(N-terminal fragment); 121 (C-terminal fragment) CT812 50 118 (maturefull length) 120 (N-terminal fragment) 122 (C-terminal fragment) CT86951 123 CT869 52 124 CT166 53 125 CT166 54 126 CT175 55 127 CT175 56 128TC0666 (CT387) 57 129 TC0666 (CT387) 58 130 TC0197 59 131 TC0197 60 132TC0261 61 133 TC0261 62 134 CT600 135 137 CT600 136 138 CT823 139 141CT823 140 142 TC0106 143 145 TC0106 144 146 TC0431 147 149 TC0431 148150 TC0210 151 153 TC0210 152 154 CT163 155 157 CT163 156 158 CT214 159161 CT214 160 162 CT721 163 165 CT721 164 166 CT127 167 169 CT127 168170

The protein of the invention, for example the variant protein or thefragment, is preferably immunogenic.

The term “immunogenic” in the context of “an immunogenic variant” and“immunogenic fragment”, is used to mean that the protein is capable ofeliciting an immune response, such as a cell-mediated and/or an antibodyresponse, against the wild-type Chlamydia protein from which it isderived, for example, when used to immunise a subject (preferably amammal, more preferably a human or a mouse). For example, the protein ofthe invention (for example, the variant or fragment) is preferablycapable of stimulating in vitro CD4+ IFNγ+ cells in splenocytes purifiedfrom mice infected with live C. trachomatis to a level comparable withthe wild-type Chlamydia protein. The protein of the invention preferablyretains the ability to elicit antibodies that recognise the wild-typeprotein. For example, the protein of the invention preferably elicitsantibodies that can bind to, and preferably neutralise the activity of,the wild-type protein. In a further embodiment, the protein of theinvention is capable of eliciting antibodies that are capable ofneutralising Chlamydia infectivity and/or virulence. In someembodiments, the antibodies are able to cross-react with the protein ofthe invention and the wild-type protein, but with no other homologousprotein (e.g. from another Chlamydia species). In other embodiments, theantibodies are cross-reactive with the wild-type protein and withhomologous proteins from other Chlamydia species. In some embodiments,the antibodies are cross-reactive with the wild-type protein and withhomologous protein from other organisms (for example from E. coli or H.influenzae). Mice immunized with the protein of the invention and thewild-type Chlamydia protein preferably show similar antigen-specificantibody titers. Antibody titres and specificities can be measured usingstandard methods available in the art. Other methods of testing theimmunogenicity of proteins are also well known in the art.

For example, the variant or fragment is preferably capable of elicitingan immune response, such as a cell-mediated and/or an antibody response,against the wild-type Chlamydia protein. In one embodiment the fragmentis capable of stimulating in vitro CD4+ IFNγ+ cells in splenocytespurified from mice infected with live C. trachomatis to a levelcomparable with the wild-type Chlamydia protein and/or retains theability to elicit antibodies that recognise the wild-type protein.

Preferably, the variant or the fragment is capable of inducing aspecific CD4-Th1 cell mediated response against the wild type Chlamydiaprotein.

The proteins of the invention can, of course, be prepared by variousmeans (e.g. recombinant expression, purification from native host,purification from cell culture, chemical synthesis etc.) and in variousforms (e.g. native, fusions, glycosylated, non-glycosylated, lipidated,non-lipidated, phosphorylated, non-phosphorylated, myristoylated,non-myristoylated, monomeric, multimeric, particulate, denatured, etc.).Generally, the recombinant fusion proteins of the present invention areprepared as a GST-fusion protein and/or a His-tagged fusion protein.

The proteins of the invention are preferably prepared in purified orsubstantially pure form (i.e. substantially free from host cell proteinsand/or other Chlamydia proteins), and are generally at least about 50%pure (by weight), and usually at least about 90% pure, i.e. less thanabout 50%, and more preferably less than about 10% (e.g. 5%) of acomposition is made up of other expressed polypeptides. Thus theantigens in the compositions are separated from the whole organism withwhich the molecule is expressed.

Whilst expression of the proteins of the invention may take place inChlamydia, the invention preferably utilises a heterologous host. Theheterologous host may be prokaryotic (e.g. a bacterium) or eukaryotic.It is preferably E. coli, but other suitable hosts include Bacillussubtilis, Vibrio cholerae, Salmonella typhi, Salmonella typhimurium,Neisseria lactamica, Neisseria cinerea, Mycobacteria (e.g. M.tuberculosis), yeasts, etc.

The term “polypeptide” or “protein” refers to amino acid polymers of anylength. The polymer may be linear or branched, it may comprise modifiedamino acids, and it may be interrupted by non-amino acids. The termsalso encompass an amino acid polymer that has been modified naturally orby intervention; for example, disulfide bond formation, glycosylation,lipidation, acetylation, phosphorylation, or any other manipulation ormodification, such as conjugation with a labeling component. Alsoincluded are, for example, polypeptides containing one or more analogsof an amino acid (including, for example, unnatural amino acids, etc.),as well as other modifications known in the art. Polypeptides can occuras single chains or associated chains.

The invention provides polypeptides comprising a sequence -P-Q- or-Q-P-, wherein: -P- is an amino acid sequence as defined above and -Q-is not a sequence as defined above i.e. the invention provides fusionproteins. Where the N-terminus codon of -P- is not ATG, but this codonis not present at the N-terminus of a polypeptide, it will be translatedas the standard amino acid for that codon rather than as a Met. Wherethis codon is at the N-terminus of a polypeptide, however, it will betranslated as Met. Examples of -Q- moieties include, but are not limitedto, histidine tags (i.e. His_(n) where n=3, 4, 5, 6, 7, 8, 9, 10 ormore), maltose-binding protein, or glutathione-S-transferase (GST).

Proteins of the invention may be attached to a solid support. They maycomprise a detectable label (e.g. a radioactive or fluorescent label, ora biotin label).

Antibodies

The proteins of the invention induce antibodies that may be used as avaccine capable of neutralising the activity of infectious EB. Theantibodies may alternatively be used for the diagnosis of Chlamydiainfection. Thus, the invention provides antibodies for use in thetreatment, prevention or diagnosis of Chlamydia infection. Preferably,the infection is by C. trachomatis, but may alternatively be by C.psittaci, C. pecorum, C. muridarum or C. suis.

The term “antibody” includes intact immunoglobulin molecules, as well asfragments thereof which are capable of binding an antigen. These includehybrid (chimeric) antibody molecules (Winter et al., (1991) Nature349:293-99; U.S. Pat. No. 4,816,567); F(ab′)2 and F(ab) fragments and Fvmolecules; non-covalent heterodimers (Inbar et al., (1972) Proc. Natl.Acad. Sci. U.S.A. 69:2659-62; Ehrlich et al., (1980) Biochem19:4091-96); single-chain Fv molecules (sFv) (Huston et al., (1988)Proc. Natl. Acad. Sci. U.S.A. 85:5897-83); dimeric and trimeric antibodyfragment constructs; minibodies Pack et al., (1992) Biochem 31, 1579-84;Cumber et al., (1992) J. Immunology 149B, 120-26); humanized antibodymolecules (Riechmann et al., (1988) Nature 332, 323-27; Verhoeyan etal., (1988) Science 239, 1534-36; and GB 2,276,169); and any functionalfragments obtained from such molecules, as well as antibodies obtainedthrough non-conventional processes such as phage display. Preferably,the antibodies are monoclonal antibodies. Methods of obtainingmonoclonal antibodies are well known in the art. Humanised orfully-human antibodies are preferred.

The antibodies may be polyclonal or monoclonal and may be produced byany suitable means. The antibody may include a detectable label.

Also provided is a method for preparing antibodies comprising immunisinga mammal (such as a mouse or a rabbit) with a protein of the inventionand obtainining polyclonal antibodies or monoclonal antibodies byconventional techniques. For example, polyclonal antisera may beobtained by bleeding the immunized animal into a glass or plasticcontainer, incubating the blood at 25° C. for one hour, followed byincubating at 4° C. for 2-18 hours. The serum is recovered bycentrifugation (eg. 1,000 g for 10 minutes). Monoclonal antibodies maybe prepared using the standard method of Kohler & Milstein [Nature(1975) 256:495-96], or a modification thereof, or by any other suitablemethod.

Nucleic Acids

According to a further aspect, the invention provides a nucleic acidencoding a protein or antibody of the invention. In some embodiments,the nucleic acid sequence encoding a protein of the invention preferablycomprises or consists of any one of SEQ ID NOs:1, 3, 5, 7, 9, 11, 13,15, 17, 39, 41, 43, 45, 47, 49, 51, 53, 55, 135, 139, 155, 159, 163 or167, for example, of any one of SEQ ID NOs:1, 3, 5, 7, 9, 11, 13, 15,39, 41, 43 or 45. In some embodiments, the nucleic acid sequenceencoding a protein of the invention comprises or consists of any one ofSEQ ID NOs: 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91,93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121,123, 125, 127, 129, 131 and 133.

The invention also provides nucleic acid comprising nucleotide sequenceshaving sequence identity to such nucleotide sequences. Identity betweensequences is preferably determined by the Smith-Waterman homology searchalgorithm as described above. Such nucleic acids include those usingalternative codons to encode the same amino acid.

The invention also provides nucleic acid which can hybridize to thesenucleic acids. Hybridization reactions can be performed under conditionsof different “stringency”. Conditions that increase stringency of ahybridization reaction of widely known and published in the art (e.g.page 7.52 of Kaplitt, Nature Genetics (1994) 6:148). Examples ofrelevant conditions include (in order of increasing stringency):incubation temperatures of 25° C., 37° C., 50° C., 55° C. and 68° C.;buffer concentrations of 10×SSC, 6×SSC, 1×SSC, 0.1×SSC (where SSC is0.15 M NaCl and 15 mM citrate buffer) and their equivalents using otherbuffer systems; formamide concentrations of 0%, 25%, 50%, and 75%;incubation times from 5 minutes to 24 hours; 1, 2, or more washingsteps; wash incubation times of 1, 2, or 15 minutes; and wash solutionsof 6×SSC, 1×SSC, 0.1×SSC, or de-ionized water. Hybridization techniquesand their optimization are well known in the art (e.g. see U.S. Pat. No.5,707,829, Current Protocols in Molecular Biology (F. M. Ausubel et al.eds., 1987) Supplement 30, Kaplitt, Nature Genetics (1994) 6:148, and WO94/03622, etc.).

The nucleic acid may be used in hybridisation reactions (e.g. Northernor Southern blots, or in nucleic acid microarrays or ‘gene chips’) or inamplification reactions (e.g. PCR, SDA, SSSR, LCR, NASBA, TMA) etc.

The invention also provides a nucleic acid comprising sequencescomplementary to those described above (e.g. for antisense or probing,or for use as primers). In one embodiment, the nucleic acid iscomplementary to the full length of the nucleic acid described above.

Nucleic acid according to the invention may be labelled e.g. with aradioactive or fluorescent label. This is particularly useful where thenucleic acid is to be used as a primer or probe e.g. in PCR, LCR or TMA.

The term “nucleic acid” includes in general means a polymeric form ofnucleotides of any length, which contain deoxyribonucleotides,ribonucleotides, and/or their analogs. It includes DNA, RNA, DNA/RNAhybrids. It also includes DNA or RNA analogs, such as those containingmodified backbones (e.g. peptide nucleic acids (PNAs) orphosphorothioates) or modified bases. Thus the invention includes mRNA,ribozymes, DNA, cDNA, recombinant nucleic acids, branched nucleic acids,plasmids, vectors, probes, primers, etc. Where nucleic acid of theinvention takes the form of RNA, it may or may not have a 5′ cap.

Nucleic acids of the invention can take various forms (e.g. singlestranded, double stranded, vectors, primers, probes etc.). Unlessotherwise specified or required, any embodiment of the invention thatutilizes a nucleic acid may utilize both the double-stranded form andeach of two complementary single-stranded forms which make up thedouble-stranded form. Primers and probes are generally single-stranded,as are antisense nucleic acids.

Nucleic acids of the invention are preferably prepared in substantiallypure form (i.e. substantially free from naturally-occurring nucleicacids, particularly from chlamydial or other host cell nucleic acids),generally being at least about 50% pure (by weight), and usually atleast about 90% pure.

Nucleic acids of the invention may be prepared in many ways e.g. bychemical synthesis (e.g. phosphoramidite synthesis of DNA) in whole orin part, by digesting longer nucleic acids using nucleases (e.g.restriction enzymes), by joining shorter nucleic acids or nucleotides(e.g. using ligases or polymerases), from genomic or cDNA libraries,etc.

The invention provides vectors comprising nucleotide sequences of theinvention (e.g. cloning or expression vectors) and host cellstransformed with such vectors. Nucleic acids of the invention may bepart of a vector i.e. part of a nucleic acid construct designed fortransduction/transfection of one or more cell types. Vectors may be, forexample, “cloning vectors” which are designed for isolation, propagationand replication of inserted nucleotides, “expression vectors” which aredesigned for expression of a nucleotide sequence in a host cell, “viralvectors” which are designed to result in the production of a recombinantvirus or virus-like particle, or “shuttle vectors”, which comprise theattributes of more than one type of vector. Preferred vectors areplasmids.

Also provided is a host cell comprising a nucleic acid of the invention.A “host cell” includes an individual cell or cell culture which can beor has been a recipient of exogenous nucleic acid. Host cells includeprogeny of a single host cell, and the progeny may not necessarily becompletely identical (in morphology or in total DNA complement) to theoriginal parent cell due to natural, accidental, or deliberate mutationand/or change. Host cells include cells transfected or infected in vivoor in vitro with nucleic acid of the invention, for example, with avector of the invention.

Where a nucleic acid is DNA, it will be appreciated that “U” in a RNAsequence will be replaced by “1′” in the DNA. Similarly, where a nucleicacid is RNA, it will be appreciated that “T” in a DNA sequence will bereplaced by “U” in the RNA.

The term “complement” or “complementary” when used in relation tonucleic acids refers to Watson-Crick base pairing. Thus the complementof C is G, the complement of G is C, the complement of A is T (or U),and the complement of T (or U) is A. It is also possible to use basessuch as I (the purine inosine) e.g. to complement pyrimidines (C or T).

Nucleic acids of the invention can be used, for example: to producepolypeptides; as hybridization probes for the detection of nucleic acidin biological samples; to generate additional copies of the nucleicacids; to generate ribozymes or antisense oligonucleotides; assingle-stranded DNA primers or probes; or as triple-strand formingoligonucleotides.

The invention provides a process for producing nucleic acid of theinvention, wherein the nucleic acid is synthesised in part or in wholeusing chemical means.

For certain embodiments of the invention, nucleic acids are preferablyat least 24 nucleotides in length (e.g. 60, 120, 240, 390, 540, 720,900, 1200, 1320, 1500, 1800, 2100, 2400, 2415 nucleotides or longer).

For certain embodiments of the invention, nucleic acids are preferablyat most 2430 nucleotides in length (e.g. 2427, 2394, 2250, 2034, 1450,1300, 1150, 1000, 850, 700, 500 nucleotides or shorter).

Primers and probes of the invention, and other nucleic acids used forhybridization, are preferably between 10 and 30 nucleotides in length(e.g. 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,26, 27, 28, 29, or 30 nucleotides).

Immunogenic Compositions and Medicaments

The protein, antibody, and/or nucleic acid or medicament may be in theform of a composition. These compositions may be suitable as immunogeniccompositions (e.g. vaccines), or as diagnostic reagents.

Preferably, the composition is an immunogenic composition. It isparticularly advantageous to use a protein of the invention in animmunogenic composition such as a vaccine. It is also envisaged that theimmunogenic composition may comprise a nucleic acid which encodes aprotein of the invention such that the protein is generated in vivo.

An immunogenic composition of the invention comprises a protein,antibody, nucleic acid, vector and/or host cell according to theinvention. Immunogenic compositions according to the invention mayeither be prophylactic (i.e. to prevent infection) or therapeutic (i.e.to treat infection), but will typically be prophylactic. Where theimmunogenic composition is for prophylactic use, the human is preferablya child (e.g. a toddler or infant) or a teenager; where the immunogeniccomposition is for therapeutic use, the human is preferably a teenageror an adult. An immunogenic composition intended for children may alsobe administered to adults e.g. to assess safety, dosage, immunogenicity,etc.

In some embodiments, the immunogenic composition is for treatment orprevention of Chlamydia infection or an associated condition (e.g.trachoma, blindness, cervicitis, pelvic inflammatory disease,infertility, ectopic pregnancy, chronic pelvic pain, salpingitis,urethritis, epididymitis, infant pneumonia, patients infected withcervical squamous cell carcinoma, and/or HIV infection, etc.),preferably, C. trachomatis infection. The immunogenic composition may beeffective against C. pneumoniae.

Immunogenic compositions used as vaccines comprise an immunologicallyeffective amount of the protein of the invention, as well as any othercomponents, as needed. By ‘immunologically effective amount’, it ismeant that the administration of that amount to an individual, either ina single dose or as part of a series, is effective for treatment orprevention. This amount varies depending upon the health and physicalcondition of the individual to be treated, age, the taxonomic group ofthe individual to be treated (e.g. non-human primate, primate, etc.),the capacity of the individual's immune system to synthesise antibodies,the degree of protection desired, the formulation of the vaccine, thetreating doctor's assessment of the medical situation, and otherrelevant factors. It is expected that the amount will fall in arelatively broad range that can be determined through routine trials.

Antigens in the composition will typically be present at a concentrationof at least 1 μg/ml each.

In general, the concentration of any given antigen will be sufficient toelicit an immune response against that antigen.

Dosage treatment can be a single dose schedule or a multiple doseschedule. Multiple doses may be used in a primary immunisation scheduleand/or in a booster immunisation schedule. In a multiple dose schedulethe various doses may be given by the same or different routes e.g. aparenteral prime and mucosal boost, a mucosal prime and parenteralboost, etc. Multiple doses will typically be administered at least 1week apart (e.g. about 2 weeks, about 3 weeks, about 4 weeks, about 6weeks, about 8 weeks, about 10 weeks, about 12 weeks, about 16 weeks,etc.). In some embodiments, three or more doses are provided (forexample, three, four or five) doses. In some embodiments, three dosesare given intramuscularly at 2 week-intervals, for example, three dosesof 10-20 μg of each protein, at 2 week-intervals, given intramuscularly.

The pH of an immunogenic composition is preferably between 6 and 8,preferably about 7. pH may be maintained by the use of a buffer. Thecomposition may be sterile and/or pyrogen-free. The composition may beisotonic with respect to humans.

Immunogenic compositions of the invention will generally be administereddirectly to a patient. Direct delivery may be accomplished by parenteralinjection (e.g. subcutaneously, intraperitoneally, intravenously,intramuscularly, or to the interstitial space of a tissue), ormucosally, such as by rectal, oral (e.g. tablet, spray), vaginal,topical, transdermal (See e.g. WO99/27961) or transcutaneous (See e.g.WO02/074244 and WO02/064162), intranasal (See e.g. WO03/028760), ocular,aural, pulmonary or other mucosal administration.

Chlamydia infections affect various areas of the body and so theimmunogenic compositions of the invention may be prepared in variousforms. For example, the compositions may be prepared as injectables,either as liquid solutions or suspensions. Solid forms suitable forsolution in, or suspension in, liquid vehicles prior to injection canalso be prepared (e.g. a lyophilised composition).

The composition may be prepared for topical administration e.g. as anointment, cream or powder. The composition may be prepared for oraladministration e.g. as a tablet or capsule, or as a syrup (optionallyflavoured). The composition may be prepared for pulmonary administratione.g. as an inhaler, using a fine powder or a spray. The composition maybe prepared as a suppository or pessary. The composition may be preparedfor nasal, aural or ocular administration e.g. as drops.

The invention also provides a delivery device pre-filled with animmunogenic composition of the invention.

The invention also provides a kit comprising a first component and asecond component wherein neither the first component nor the secondcomponent is a composition of the invention as described herein, butwherein the first component and the second component can be combined toprovide a composition of the invention as described herein. The kit mayfurther include a third component comprising one or more of thefollowing: instructions, syringe or other delivery device, adjuvant, orpharmaceutically acceptable formulating solution.

A composition as described above may alternatively and/or additionallybe used for diagnosis of chlamydia infection.

Combinations with Other Antigens

The therapeutic or diagnostic efficiency of a Chlamydia antigen may beimproved by combination with a different Chlamydia antigen. For example,the immunogenicity of a protein of the invention may be improved bycombination with another protein of the invention or with another knownChlamydia antigen. The invention thus includes an immunogeniccomposition comprising a combination of Chlamydia antigens, saidcombination comprising a protein of the invention in combination withone or more additional Chlamydia antigens. The one or more additionalChlamydia antigens that are present in the composition may be in theform of a protein or nucleic acid or any other suitable form. A proteinof the invention may be combined with one or more (e.g. 2, 3, 4, 5, 6,7, 8, 9, 10, 15, 20 or more) different proteins of the invention and/orwith one or more (e.g. 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20 or more) otherknown Chlamydia antigens. For example, an immunogenic composition isprovided comprising two or more (e.g. 3, 4, 5, 6, 7, 8, 9, 10, 15, 20 ormore) proteins of the invention. The proteins of the invention mayalternatively and/or additionally be provided in the composition in theform of their corresponding nucleic acids, vectors, host cells, etc.Also provided is a protein or nucleic acid of the invention for a use asdescribed above, wherein the protein or nucleic acid is for use incombination with one or more additional Chlamydia antigens (or theirencoding nucleic acids). The one or more additional antigens (e.g. 2, 3,4, 5, 6, 7 or more additional antigens) may be administeredsimultaneously, separately or sequentially with the protein or nucleicacid of the invention, for example as a combined preparation.

Likewise, the antibodies of the invention may be used in combinationwith one or more antibodies specific for one or more additionalChlamydia antigens for use in diagnosis of Chlamydia infections.

In one embodiment, one or more of the additional Chlamydia antigens isselected from the antigens presented in Table 2, or their variants. Forexample, one or more (for example, all) of the additional antigens areselected from the Chlamydia trachomatis antigens listed in Table 2, butmay alternatively or additionally be selected from the Chlamydiapneumoniae antigens listed in Table 2. In some embodiments, the one ormore (for example, all) of the additional antigens are selected from theChlamydia trachomatis antigens and/or Chlamydia pneumoniae antigenslisted in Table 2 and CT387, CT812, CT869, CT166, CT175, CT163, CT214,CT721 and CT127. In one embodiment, one or more of the one or moreadditional antigens are selected from CT372, CT443, CT043, CT153, CT279,CT601, CT711, CT114, CT480, CT456, CT381, CT089, CT734, CT016, CT600,CT823, CT387, CT812, CT869, CT166, CT175, CT163, CT214, CT721 and CT127(or their variants), for example, from CT372, CT443, CT043, CT153,CT279, CT601, CT711, CT114, CT480, CT456, CT381, CT089, CT734, CT016,CT600 and CT823. These additional antigens are listed in Table 2 andtheir sequences are set out in the “Sequences” section that followsTable 2. In one embodiment, one or more proteins of the invention iscombined with CT089. In another embodiment, one or more proteins of theinvention is combined with CT089 and CT381 (or their variants). In someembodiments, the C-terminal fragment of CT812 “CT812C” (for example, aprotein comprising or consisting of the amino acid sequence set out inSEQ ID NO:122 or a fragment or variant thereof) is used instead of fulllength CT812.

In some embodiments, the following combinations of antigens (or theirvariants) are used: CT733+CT601, CT733+CT279, CT733+CT443, CT733+CT372,CT733+CT456, CT733+CT381, CT153+CT601, CT153+CT279, CT153+CT443,CT153+CT372, CT153+CT456, CT153+CT381, CT601+CT443, CT601+CT372,CT601+CT456, CT601+CT381, CT279+CT443, CT279+CT372, CT279+CT456,CT279+CT381, CT443+CT372, CT443+CT456, CT443+CT381, CT372+CT456,CT372+CT381, CT387+CT812+CT869, CT387+CT812C+CT869. These combinationsmay be used in the absence of any other chlamydia antigens or in thepresence of one or more additional chlamydia antigens. Particularlypreferred combinations are: (i) CT279+CT601; (ii) CT372+CT443; (iii)CT733+CT153; (iv) CT456+CT381; (v) CT279+CT601+CT733+CT153; (vi)CT279+CT601+CT372+CT443; (vii) CT823+CT733+CT043+CT456; (viii)CT387+CT812+CT869; and (ix) CT387+CT812C+CT869 (or their variants).

The human serovariants (“serovars”) of C. trachomatis are divided intotwo biovariants (“biovars”). Serovars A-K elicit epithelial infectionsprimarily in the ocular tissue (A-C) or urogenital tract (D-K). SerovarsLI, L2 and L3 are the agents of invasive lymphogranuloma venereum (LGV).In some embodiments, one or more of the additional Chlamydial antigensmay, for example, be of any of Serovars A-K or L1, L2 or L3. One or moreof the additional Chlamydia antigens is preferably from C. trachomatisserovar D, or from another epidemiologically prevalent serotype.

In some embodiments, one or more of the additional Chlamydia antigens isa homologous antigen from C. pneumoniae, C. psittaci, C. pecorum, C.muridarum or C. suis.

In some embodiments, TC0551 (the C. muridarum homologue of CT279) isused in place of the C. trachomatis protein. C. muridarum is the mouseadapted strain of Chlamydia trachomatis. Although C. muridarum is not ahuman pathogen, infection of mice with C. muridarum phenotypicallymimics many aspects of C. trachomatis infection in humans and isfrequently used to measure immunoprotective responses against C.trachomatis. In some embodiments, TC0890 (the C. muridarum homologue ofCT601) is used in place of the C. trachomatis protein. In someembodiments, TC0651 (the C. muridarum homologue of CT372) is used inplace of the C. trachomatis protein. In some embodiments, TC0727 (the C.muridarum homologue of CT443) is used in place of the C. trachomatisprotein. In some embodiments, TC0106 (the C. muridarum homologue ofCT733) is used in place of the C. trachomatis protein. In someembodiments, TC0431 (the C. muridarum homologue of CT153) is used inplace of the C. trachomatis protein. In some embodiments, TC0660 (the C.muridarum homologue of C1381) is used in place of the C. trachomatisprotein. In some embodiments, TC0741 (the C. muridarum homologue ofCT456) is used in place of the C. trachomatis protein. In someembodiments, TC0210 (the C. muridarum homologue of CT823) is used inplace of the C. trachomatis protein. In some embodiments, TC0666 (the C.muridarum homologue of CT387) is used in place of the C. trachomatisprotein. TC0666 is annotated as a hypothetical protein. In someembodiments, TC0197 (the C. muridarum homologue of CT812) is used inplace of the C. trachomatis protein. TC0197 is annotated as polymorphicmembrane protein D family protein. In some embodiments, TC0261 (the C.muridarum homologue of CT869) is used in place of the C. trachomatisprotein. TC0261 is annotated as polymorphic membrane protein E/F familyprotein. In some embodiments, TC0313 (the C. muridarum homologue ofCT043) is used in place of the C. trachomatis protein. In someembodiments, TC0889 (the C. muridarum homologue of CT600) is used inplace of the C. trachomatis protein. In some embodiments, TC0210 (the C.muridarum homologue of CT823) is used in place of the C. trachomatisprotein. In some embodiments in which the composition comprises a singleChlamydia antigen, the C. muridarum homologue is used in place of thesingle C. trachomatis antigen. In some embodiments in which thecomposition comprises a combination of Chlamydia antigens, the C.muridarum homologue is used in place of one or more (for example, 1, 2,3, 4, 5, 6, 7, 8, 9, 10) or all C. trachomatis antigens.

Advantageous combinations of the invention are those in which two ormore antigens (for example, two, three or four antigens) actsynergistically. Thus, the protection against Chlamydia achieved bytheir combined administration exceeds that expected by mere addition oftheir individual protective efficacy.

In some embodiments, the one or more additional Chlamydia antigens maycomprise an amino acid sequence: (a) which is a variant of a Table 2antigen (i.e. has 50% or more identity (e.g. 60%, 65%, 70%, 75%, 80%,85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) toa sequence presented in Table 2); and/or (b) comprising a fragment of atleast ‘n’ consecutive amino acids of a sequence presented in Table 2 orof a variant of a Table 2 antigen, wherein ‘n’ is 7 or more (e.g. 8, 10,12, 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200,250, 350, 450, 550, 650, 750, 780, 800 or more). Preferred fragments of(b) comprise an epitope from a sequence presented in Table 2.Preferably, the epitope is a MHC class II epitope, for example, a CD4+ Tcell epitope. Other preferred fragments lack one or more amino acids(e.g. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) from theC-terminus and/or one or more amino acids (e.g. 1, 2, 3, 4, 5, 6, 7, 8,9, 10, 15, 20, 25 or more) from the N-terminus of a sequence presentedin Table 2, while retaining at least one epitope of a sequence presentedin Table 2. Other fragments omit one or more protein domains. When anadditional Chlamydia antigen comprises a sequence that is not identicalto a complete sequence from Table 2 (e.g. when it comprises a sequencewith less than 100% sequence identity thereto, or when it comprises afragment thereof), it is preferred in each individual instance that theadditional Chlamydia antigen can elicit an antibody that recognises aprotein having the complete sequence from the Table 2 antigen from whichit is derived.

In some embodiments, the combination of two or more chlamydia antigensis provided as a combined preparation for simultaneous, separate orsequential administration. The invention also provides a kit comprisinga protein of the invention and one or more additional antigens forsimultaneous, separate or sequential administration.

The Chlamydia antigens used in the invention may be present in thecomposition as individual separate polypeptides. Alternatively, thecombination may be present as a hybrid polypeptide in which two or more(i.e. 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or20 or more) of the antigens are expressed as a single polypeptide chain.Hybrid polypeptides offer two principal advantages: first, a polypeptidethat may be unstable or poorly expressed on its own can be assisted byadding a suitable hybrid partner that overcomes the problem; second,commercial manufacture is simplified as only one expression andpurification need be employed in order to produce two polypeptides whichare both antigenically useful. Different hybrid polypeptides may bemixed together in a single formulation. Within such combinations, aChlamydia trachomatis antigen may be present in more than one hybridpolypeptide and/or as a non-hybrid polypeptide. It is preferred,however, that an antigen is present either as a hybrid or as anon-hybrid, but not as both.

Hybrid polypeptides can be represented by the formulaNH₂-A-{-X-L-}_(n)-B-COOH, wherein: at least one X is an amino acidsequence of a Chlamydia protein according to the invention as describedabove; L is an optional linker amino acid sequence; A is an optionalN-terminal amino acid sequence; B is an optional C-terminal amino acidsequence; n is an integer of 2 or more (e.g. 2, 3, 4, 5, 6, etc.).Usually n is 2 or 3.

If a -X- moiety has a leader peptide sequence in its wild-type form,this may be included or omitted in the hybrid protein. In someembodiments, the leader peptides will be deleted except for that of the-X- moiety located at the N-terminus of the hybrid protein i.e. theleader peptide of X₁ will be retained, but the leader peptides of X₂ . .. X_(n) will be omitted. This is equivalent to deleting all leaderpeptides and using the leader peptide of X₁ as moiety -A-.

For each n instances of {-X-L-}, linker amino acid sequence -L- may bepresent or absent. For instance, when n=2 the hybrid may beNH₂-X₁-L₁-X₂-L₂-COOH, NH₂-X₁-X₂-COOH, NH₂-X₁-L₁-X₂-COOH,NH₂-X₁-X₂-L₂-COOH, etc. Linker amino acid sequence(s) -L- will typicallybe short (e.g. 20 or fewer amino acids i.e. 20, 19, 18, 17, 16, 15, 14,13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1). Examples comprise shortpeptide sequences which facilitate cloning, poly-glycine linkers (i.e.comprising Gly_(n) where n=2, 3, 4, 5, 6, 7, 8, 9, 10 or more), andhistidine tags (i.e. His_(n) where n=3, 4, 5, 6, 7, 8, 9, 10 or more).Other suitable linker amino acid sequences will be apparent to thoseskilled in the art. A useful linker is GSGGGG, with the Gly-Serdipeptide being formed from a BamHI restriction site, thus aidingcloning and manipulation, and the (Gly)₄ tetrapeptide being a typicalpoly-glycine linker.

-A- is an optional N-terminal amino acid sequence. This will typicallybe short (e.g. 40 or fewer amino acids i.e. 40, 39, 38, 37, 36, 35, 34,33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16,15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1). Examples includeleader sequences to direct protein trafficking, or short peptidesequences which facilitate cloning or purification (e.g. histidine tagsi.e. His_(n) where n=3, 4, 5, 6, 7, 8, 9, 10 or more). Other suitableN-terminal amino acid sequences will be apparent to those skilled in theart. If X₁ lacks its own N-terminus methionine, -A- is preferably anoligopeptide (e.g. with 1, 2, 3, 4, 5, 6, 7 or 8 amino acids) whichprovides a N-terminus methionine.

-B- is an optional C-terminal amino acid sequence. This will typicallybe short (e.g. 40 or fewer amino acids i.e. 39, 38, 37, 36, 35, 34, 33,32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15,14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1). Examples includesequences to direct protein trafficking, short peptide sequences whichfacilitate cloning or purification (e.g. comprising histidine tags i.e.His_(n) where n=3, 4, 5, 6, 7, 8, 9, 10 or more), or sequences whichenhance protein stability. Other suitable C-terminal amino acidsequences will be apparent to those skilled in the art.

Where hybrid polypeptides are used, the individual antigens within thehybrid (i.e. individual -X- moieties) may be from one or more strains.Where n=2, for instance, X₂ may be from the same strain as X₁ or from adifferent strain. Where n=3, the strains might be (i) X₁=X₂=X₃ (ii)X₁=X₂≠X₃ (iii) X₁≠X₂=X₃ (iv) X₁≠X₂≠X₃ or (v) X₁=X₃≠X₂, etc.

The invention also provides a nucleic acid encoding a hybrid polypeptideof the invention. Furthermore, the invention provides a nucleic acidwhich can hybridise to this nucleic acid, preferably under “highstringency” conditions (e.g. 65° C. in a 0.1×SSC, 0.5% SDS solution).

Further Components of the Composition

Compositions may thus be pharmaceutically acceptable. They will usuallyinclude components in addition to the antigens e.g. they typicallyinclude one or more pharmaceutical carrier(s) and/or excipient(s). Athorough discussion of such components is available in Remington TheScience and Practice of Pharmacy.

Compositions will generally be administered to a mammal in aqueous form.Prior to administration, however, the composition may have been in anon-aqueous form. For instance, although some vaccines are manufacturedin aqueous form, then filled and distributed and administered also inaqueous form, other vaccines are lyophilised during manufacture and arereconstituted into an aqueous form at the time of use. Thus acomposition of the invention may be dried, such as a lyophilisedformulation.

The composition may include preservatives such as thiomersal or2-phenoxyethanol. It is preferred, however, that the vaccine should besubstantially free from (i.e. less than 5 μg/ml) mercurial material e.g.thiomersal-free. Vaccines containing no mercury arc more preferred.Preservative-free vaccines are particularly preferred.

To control tonicity, it is preferred to include a physiological salt,such as a sodium salt. Sodium chloride (NaCl) is preferred, which may bepresent at between 1 and 20 mg/ml e.g. about 10+2 mg/ml NaCl. Othersalts that may be present include potassium chloride, potassiumdihydrogen phosphate, disodium phosphate dehydrate, magnesium chloride,calcium chloride, etc.

Compositions will generally have an osmolality of between 200 mOsm/kgand 400 mOsm/kg, preferably between 240-360 mOsm/kg, and will morepreferably fall within the range of 290-310 mOsm/kg.

Compositions may include one or more buffers. Typical buffers include: aphosphate buffer; a Tris buffer; a borate buffer; a succinate buffer; ahistidine buffer (particularly with an aluminum hydroxide adjuvant); ora citrate buffer. Buffers will typically be included in the 5-20 mMrange.

The pH of a composition will generally be between 5.0 and 8.1, and moretypically between 6.0 and 8.0 e.g. 6.5 and 7.5, or between 7.0 and 7.8.

The composition is preferably sterile. The composition is preferablynon-pyrogenic e.g. containing <1 EU (endotoxin unit, a standard measure)per dose, and preferably <0.1 EU per dose. The composition is preferablygluten free.

The composition may include material for a single immunisation, or mayinclude material for multiple immunisations (i.e. a ‘multidose’ kit).The inclusion of a preservative is preferred in multidose arrangements.As an alternative (or in addition) to including a preservative inmultidose compositions, the compositions may be contained in a containerhaving an aseptic adaptor for removal of material.

Human vaccines are typically administered in a dosage volume of about0.5 ml, although a half dose (i.e. about 0.25 ml) may be administered tochildren.

Immunogenic compositions of the invention may also comprise one or moreimmunoregulatory agents. Preferably, one or more of the immunoregulatoryagents include one or more adjuvants. The adjuvants may include a TH1adjuvant and/or a TH2 adjuvant, further discussed below.

Adjuvants which may be used in compositions of the invention include,but are not limited to:

A. Mineral-Containing Compositions

Mineral containing compositions suitable for use as adjuvants in theinvention include mineral salts, such as aluminium salts and calciumsalts (or mixtures thereof). Calcium salts include calcium phosphate(e.g. the “CAP” particles disclosed in U.S. Pat. No. 6,355,271).Aluminum salts include hydroxides, phosphates, sulfates, etc., with thesalts taking any suitable form (e.g. gel, crystalline, amorphous, etc.).Adsorption to these salts is preferred. The mineral containingcompositions may also be formulated as a particle of metal salt[WO00/23105].

The adjuvants known as aluminum hydroxide and aluminum phosphate may beused. These names are conventional, but are used for convenience only,as neither is a precise description of the actual chemical compoundwhich is present (e.g. see chapter 9 of Vaccine Design . . . (1995) eds.Powell & Newman. ISBN: 030644867X. Plenum). The invention can use any ofthe “hydroxide” or “phosphate” adjuvants that are in general use asadjuvants. The adjuvants known as “aluminium hydroxide” are typicallyaluminium oxyhydroxide salts, which are usually at least partiallycrystalline. The adjuvants known as “aluminium phosphate” are typicallyaluminium hydroxyphosphates, often also containing a small amount ofsulfate (i.e. aluminium hydroxyphosphate sulfate). They may be obtainedby precipitation, and the reaction conditions and concentrations duringprecipitation influence the degree of substitution of phosphate forhydroxyl in the salt.

A fibrous morphology (e.g. as seen in transmission electron micrographs)is typical for aluminium hydroxide adjuvants. The pI of aluminiumhydroxide adjuvants is typically about 11 i.e. the adjuvant itself has apositive surface charge at physiological pH. Adsorptive capacities ofbetween 1.8-2.6 mg protein per mg Al⁺⁺⁺ at pH 7.4 have been reported foraluminium hydroxide adjuvants.

Aluminium phosphate adjuvants generally have a PO₄/Al molar ratiobetween 0.3 and 1.2, preferably between 0.8 and 1.2, and more preferably0.95±0.1. The aluminium phosphate will generally be amorphous,particularly for hydroxyphosphate salts. A typical adjuvant is amorphousaluminium hydroxyphosphate with PO₄/Al molar ratio between 0.84 and0.92, included at 0.6 mg Al³⁺/ml. The aluminium phosphate will generallybe particulate (e.g. plate-like morphology as seen in transmissionelectron micrographs). Typical diameters of the particles are in therange 0.5-20 μm (e.g. about 5-10 μm) after any antigen adsorption.Adsorptive capacities of between 0.7-1.5 mg protein per mg Al⁺⁺⁺ at pH7.4 have been reported for aluminium phosphate adjuvants.

The point of zero charge (PZC) of aluminium phosphate is inverselyrelated to the degree of substitution of phosphate for hydroxyl, andthis degree of substitution can vary depending on reaction conditionsand concentration of reactants used for preparing the salt byprecipitation. PZC is also altered by changing the concentration of freephosphate ions in solution (more phosphate=more acidic PZC) or by addinga buffer such as a histidine buffer (makes PZC more basic). Aluminiumphosphates used according to the invention will generally have a PZC ofbetween 4.0 and 7.0, more preferably between 5.0 and 6.5 e.g. about 5.7.

Suspensions of aluminium salts used to prepare compositions of theinvention may contain a buffer (e.g. a phosphate or a histidine or aTris buffer), but this is not always necessary. The suspensions arepreferably sterile and pyrogen-free. A suspension may include freeaqueous phosphate ions e.g. present at a concentration between 1.0 and20 mM, preferably between 5 and 15 mM, and more preferably about 10 mM.The suspensions may also comprise sodium chloride.

The invention can use a mixture of both an aluminium hydroxide and analuminium phosphate. In this case there may be more aluminium phosphatethan hydroxide e.g. a weight ratio of at least 2:1 e.g. ≧5:1, ≧6:1,≧7:1, ≧8:1, ≧9:1, etc.

The concentration of Al⁺⁺⁺ in a composition for administration to apatient is preferably less than 10 mg/ml e.g. ≦5 mg/ml, ≦4 mg/ml, ≦3mg/ml, ≦mg/ml, ≦1 mg/ml, etc. A preferred range is between 0.3 and 1mg/ml. A maximum of 0.85 mg/dose is preferred.

Aluminium phosphates are particularly preferred, particularly incompositions which include a H. influenzae saccharide antigen, and atypical adjuvant is amorphous aluminium hydroxyphosphate with PO₄/Almolar ratio between 0.84 and 0.92, included at 0.6 mg Al³⁺/ml.Adsorption with a low dose of aluminium phosphate may be used e.g.between 50 and 100 μg Al³⁺ per conjugate per dose. Where there is morethan one conjugate in a composition, not all conjugates need to beadsorbed.

B. Oil Emulsions

Oil emulsion compositions suitable for use as adjuvants in the inventioninclude squalene-water emulsions, such as MF59 [Chapter 10 of VaccineDesign . . . (1995) eds. Powell & Newman. ISBN: 030644867X. Plenum; seealso WO90/14837] (5% Squalene, 0.5% Tween 80, and 0.5% Span 85,formulated into submicron particles using a microfluidizer). CompleteFreund's adjuvant (CFA) and incomplete Freund's adjuvant (IFA) may alsobe used.

Various oil-in-water emulsion adjuvants are known, and they typicallyinclude at least one oil and at least one surfactant, with the oil(s)and surfactant(s) being biodegradable (metabolizable) and biocompatible.The oil droplets in the emulsion are generally less than 5 μm indiameter, and ideally have a sub-micron diameter, with these small sizesbeing achieved with a microfluidiser to provide stable emulsions.Droplets with a size less than 220 nm are preferred as they can besubjected to filter sterilization.

The emulsion can comprise oils such as those from an animal (such asfish) or vegetable source. Sources for vegetable oils include nuts,seeds and grains. Peanut oil, soybean oil, coconut oil, and olive oil,the most commonly available, exemplify the nut oils. Jojoba oil can beused e.g. obtained from the jojoba bean. Seed oils include saffloweroil, cottonseed oil, sunflower seed oil, sesame seed oil and the like.In the grain group, corn oil is the most readily available, but the oilof other cereal grains such as wheat, oats, rye, rice, teff, triticaleand the like may also be used. 6-10 carbon fatty acid esters of glyceroland 1,2-propanediol, while not occurring naturally in seed oils, may beprepared by hydrolysis, separation and esterification of the appropriatematerials starting from the nut and seed oils. Fats and oils frommammalian milk are metabolizable and may therefore be used in thepractice of this invention. The procedures for separation, purification,saponification and other means necessary for obtaining pure oils fromanimal sources are well known in the art. Most fish containmetabolizable oils which may be readily recovered. For example, codliver oil, shark liver oils, and whale oil such as spermaceti exemplifyseveral of the fish oils which may be used herein. A number of branchedchain oils are synthesized biochemically in 5-carbon isoprene units andare generally referred to as terpenoids. Shark liver oil contains abranched, unsaturated terpenoids known as squalene,2,6,10,15,19,23-hexamethyl-2,6,10,14,18,22-tetracosahexaene, which isparticularly preferred herein. Squalane, the saturated analog tosqualene, is also a preferred oil. Fish oils, including squalene andsqualane, are readily available from commercial sources or may beobtained by methods known in the art. Other preferred oils are thetocopherols (see below). Mixtures of oils can be used.

Surfactants can be classified by their ‘HLB’ (hydrophile/lipophilebalance). Preferred surfactants of the invention have a HLB of at least10, preferably at least 15, and more preferably at least 16. Theinvention can be used with surfactants including, but not limited to:the polyoxyethylene sorbitan esters surfactants (commonly referred to asthe Tweens), especially polysorbate 20 and polysorbate 80; copolymers ofethylene oxide (EO), propylene oxide (PO), and/or butylene oxide (BO),sold under the DOWFAX™ tradename, such as linear EO/PO block copolymers;octoxynols, which can vary in the number of repeating ethoxy(oxy-1,2-ethanediyl) groups, with octoxynol-9 (Triton X-100, ort-octylphenoxypolyethoxyethanol) being of particular interest;(octylphenoxy)polyethoxyethanol (IGEPAL CA-630/NP-40); phospholipidssuch as phosphatidylcholine (lecithin); nonylphenol ethoxylates, such asthe Tergitol™ NP series; polyoxyethylene fatty ethers derived fromlauryl, cetyl, stearyl and oleyl alcohols (known as Brij surfactants),such as triethyleneglycol monolauryl ether (Brij 30); and sorbitanesters (commonly known as the SPANs), such as sorbitan trioleate (Span85) and sorbitan monolaurate. Non-ionic surfactants are preferred.Preferred surfactants for including in the emulsion are Tween 80(polyoxyethylene sorbitan monooleate), Span 85 (sorbitan trioleate),lecithin and Triton X-100.

Mixtures of surfactants can be used e.g. Tween 80/Span 85 mixtures. Acombination of a polyoxyethylene sorbitan ester such as polyoxyethylenesorbitan monooleate (Tween 80) and an octoxynol such ast-octylphenoxypolyethoxyethanol (Triton X-100) is also suitable. Anotheruseful combination comprises laureth 9 plus a polyoxyethylene sorbitanester and/or an octoxynol.

Preferred amounts of surfactants (% by weight) are: polyoxyethylenesorbitan esters (such as Tween 80) 0.01 to 1%, in particular about 0.1%;octyl- or nonylphenoxy polyoxyethanols (such as Triton X-100, or otherdetergents in the Triton series) 0.001 to 0.1%, in particular 0.005 to0.02%; polyoxyethylene ethers (such as laureth 9) 0.1 to 20%, preferably0.1 to 10% and in particular 0.1 to 1% or about 0.5%.

Preferred emulsion adjuvants have an average droplets size of <1 μm e.g.≦750 nm, ≦500 nm, ≦400 nm, ≦300 nm, ≦250 nm, ≦220 nm, ≦200 nm, orsmaller. These droplet sizes can conveniently be achieved by techniquessuch as microfluidisation.

Specific oil-in-water emulsion adjuvants useful with the inventioninclude, but are not limited to:

-   -   A submicron emulsion of squalene, Tween 80, and Span 85. The        composition of the emulsion by volume can be about 5% squalene,        about 0.5% polysorbate 80 and about 0.5% Span 85. In weight        terms, these ratios become 4.3% squalene, 0.5% polysorbate 80        and 0.48% Span 85. This adjuvant is known as ‘MF59’ (WO90/14837,        Podda & Del Giudice (2003) Expert Rev Vaccines 2:197-203,        Podda (2001) Vaccine 19: 2673-2680; as described in more detail        in Chapter 10 of Vaccine Design: The Subunit and Adjuvant        Approach (eds. Powell & Newman) Plenum Press 1995 (ISBN        0-306-44867-X) and chapter 12 of Vaccine Adjuvants: Preparation        Methods and Research Protocols (Volume 42 of Methods in        Molecular Medicine series). ISBN: 1-59259-083-7. Ed. O'Hagan).        The MF59 emulsion advantageously includes citrate ions e.g. 10        mM sodium citrate buffer.    -   An emulsion of squalene, a tocopherol, and Tween 80. The        emulsion may include phosphate buffered saline. It may also        include Span 85 (e.g. at 1%) and/or lecithin. These emulsions        may have from 2 to 10% squalene, from 2 to 10% tocopherol and        from 0.3 to 3% Tween 80, and the weight ratio of        squalene:tocopherol is preferably ≦1 as this provides a more        stable emulsion. Squalene and Tween 80 may be present volume        ratio of about 5:2. One such emulsion can be made by dissolving        Tween 80 in PBS to give a 2% solution, then mixing 90m1 of this        solution with a mixture of (5 g of DL-α-tocopherol and 5 ml        squalene), then microfluidising the mixture.

The resulting emulsion may have submicron oil droplets e.g. with anaverage diameter of between 100 and 250 nm, preferably about 180 nm.

-   -   An emulsion of squalene, a tocopherol, and a Triton detergent        (e.g. Triton X-100). The emulsion may also include a 3d-MPL (see        below). The emulsion may contain a phosphate buffer.    -   An emulsion comprising a polysorbate (e.g. polysorbate 80), a        Triton detergent (e.g. Triton X-100) and a tocopherol (e.g. an        α-tocopherol succinate). The emulsion may include these three        components at a mass ratio of about 75:11:10 (e.g. 750 μg/ml        polysorbate 80, 110 μg/ml Triton X-100 and 100 m/ml α-tocopherol        succinate), and these concentrations should include any        contribution of these components from antigens. The emulsion may        also include squalene. The emulsion may also include a 3d-MPL        (see below). The aqueous phase may contain a phosphate buffer.    -   An emulsion of squalane, polysorbate 80 and poloxamer 401        (“Pluronic™ L121”). The emulsion can be formulated in phosphate        buffered saline, pH 7.4. This emulsion is a useful delivery        vehicle for muramyl dipeptides, and has been used with        threonyl-MDP in the “SAF-1” adjuvant (Allison & Byars (1992) Res        Immunol 143:519-25) (0.05-1% Thr-MDP, 5% squalane, 2.5% Pluronic        L121 and 0.2% polysorbate 80). It can also be used without the        Thr-MDP, as in the “AF” adjuvant (Hariharan et al. (1995) Cancer        Res 55:3486-9) (5% squalane, 1.25% Pluronic L121 and 0.2%        polysorbate 80). Microfluidisation is preferred.    -   An emulsion comprising squalene, an aqueous solvent, a        polyoxyethylene alkyl ether hydrophilic nonionic surfactant        (e.g. polyoxyethylene (12) cetostearyl ether) and a hydrophobic        nonionic surfactant (e.g. a sorbitan ester or mannide ester,        such as sorbitan monoleate or ‘Span 80’). The emulsion is        preferably thermoreversible and/or has at least 90% of the oil        droplets (by volume) with a size less than 200 nm        (US-2007/014805.). The emulsion may also include one or more of:        alditol; a cryoprotective agent (e.g. a sugar, such as        dodecylmaltoside and/or sucrose); and/or an alkylpolyglycoside.        Such emulsions may be lyophilized.    -   An emulsion o US-2007/014805.f squalene, poloxamer 105 and        Abil-Care (Suli et al. (2004) Vaccine 22(25-26):3464-9). The        final concentration (weight) of these components in adjuvanted        vaccines are 5% squalene, 4% poloxamer 105 (pluronic polyol) and        2% Abil-Care 85 (Bis-PEG/PPG-16/16 PEG/PPG-16/16 dimethicone;        capryl ic/capric triglyceride).    -   An emulsion having from 0.5-50% of an oil, 0.1-10% of a        phospholipid, and 0.05-5% of a non-ionic surfactant. As        described in WO95/11700, preferred phospholipid components are        phosphatidylcholine, phosphatidylethanolamine,        phosphatidylserine, phosphatidylinositol, phosphatidylglycerol,        phosphatidic acid, sphingomyelin and cardiolipin. Submicron        droplet sizes are advantageous.    -   A submicron oil-in-water emulsion of a non-metabolisable oil        (such as light mineral oil) and at least one surfactant (such as        lecithin, Tween 80 or Span 80). Additives may be included, such        as QuilA saponin, cholesterol, a saponin-lipophile conjugate        (such as GPI-0100, described in U.S. Pat. No. 6,080,725,        produced by addition of aliphatic amine to desacylsaponin via        the carboxyl group of glucuronic acid),        dimethyidioctadecylammonium bromide and/or        N,N-dioctadecyl-N,N-bis (2-hydroxyethyl)propanediamine.    -   An emulsion in which a saponin (e.g. QuilA or QS21) and a sterol        (e.g. a cholesterol) are associated as helical micelles        (WO2005/097181).    -   An emulsion comprising a mineral oil, a non-ionic lipophilic        ethoxylated fatty alcohol, and a non-ionic hydrophilic        surfactant (e.g. an ethoxylated fatty alcohol and/or        polyoxyethylene-polyoxypropylene block copolymer)        (WO2006/113373).    -   An emulsion comprising a mineral oil, a non-ionic hydrophilic        ethoxylated fatty alcohol, and a non-ionic lipophilic surfactant        (e.g. an ethoxylated fatty alcohol and/or        polyoxyethylene-polyoxypropylene block copolymer) (Wu et        al. (2004) Antiviral Res. 64(2):79-83).

In some embodiments an emulsion may be mixed with antigenextemporaneously, at the time of delivery, and thus the adjuvant andantigen may be kept separately in a packaged or distributed vaccine,ready for final formulation at the time of use. In other embodiments anemulsion is mixed with antigen during manufacture, and thus thecomposition is packaged in a liquid adjuvanted form. The antigen willgenerally be in an aqueous form, such that the vaccine is finallyprepared by mixing two liquids. The volume ratio of the two liquids formixing can vary (e.g. between 5:1 and 1:5) but is generally about 1:1.Where concentrations of components are given in the above descriptionsof specific emulsions, these concentrations are typically for anundiluted composition, and the concentration after mixing with anantigen solution will thus decrease. Where a composition is to beprepared extemporaneously prior to use (e.g. where a component ispresented in lyophilised form) and is presented as a kit, the kit maycomprise two vials, or it may comprise one ready-filled syringe and onevial, with the contents of the syringe being used to reactivate thecontents of the vial prior to injection.

Where a composition includes a tocopherol, any of the α, β, γ, δ, ε or ξtocopherols can be used, but α-tocopherols are preferred. The tocopherolcan take several forms e.g. different salts and/or isomers. Saltsinclude organic salts, such as succinate, acetate, nicotinate, etc.D-α-tocopherol and DL-α-tocopherol can both be used. Tocopherols areadvantageously included in vaccines for use in elderly patients (e.g.aged 60 years or older) because vitamin E has been reported to have apositive effect on the immune response in this patient group (Han et al.(2005) Impact of Vitamin E on Immune Function and Infectious Diseases inthe Aged at Nutrition, Immune functions and Health EuroConference,Paris, 9-10 June 2005). They also have antioxidant properties that mayhelp to stabilize the emulsions (U.S. Pat. No. 6,630,161). A preferredα-tocopherol is DL-α-tocopherol, and the preferred salt of thistocopherol is the succinate. The succinate salt has been found tocooperate with TNF-related ligands in vivo.

C. Saponin formulations (chapter 22 of Vaccine Design . . . (1995) eds.Powell & Newman. ISBN: 030644867X Plenum)

Saponin formulations may also be used as adjuvants in the invention.Saponins are a heterogeneous group of sterol glycosides and triterpenoidglycosides that are found in the bark, leaves, stems, roots and evenflowers of a wide range of plant species. Saponin from the bark of theQuillaia saponaria Molina tree have been widely studied as adjuvants.Saponin can also be commercially obtained from Smilax ornata(sarsaprilla), Gypsophilla paniculata (brides veil), and Saponariaofficinalis (soap root). Saponin adjuvant formulations include purifiedformulations, such as QS21, as well as lipid formulations, such asISCOMs. QS21 is marketed as Stimulon™.

Saponin compositions have been purified using HPLC and RP-HPLC. Specificpurified fractions using these techniques have been identified,including QS7, QS17, QS18, QS21, QH-A, QH-B and QH-C. Preferably, thesaponin is QS21. A method of production of QS21 is disclosed in U.S.Pat. No. 5,057,540. Saponin formulations may also comprise a sterol,such as cholesterol (WO96/33739).

Combinations of saponins and cholesterols can be used to form uniqueparticles called immunostimulating complexs (ISCOMs) (chapter 23 ofVaccine Design . . . (1995) eds. Powell & Newman. ISBN: 030644867X.Plenum). ISCOMs typically also include a phospholipid such asphosphatidylethanolamine or phosphatidylcholine. Any known saponin canbe used in ISCOMs. Preferably, the ISCOM includes one or more of QuilA,QHA & QHC. ISCOMs are further described in Podda & Del Giudice (2003)Expert Rev Vaccines 2:197-203; Podda (2001) Vaccine 19: 2673-2680;Vaccine Design: The Subunit and Adjuvant Approach (eds. Powell & Newman)Plenum Press 1995 (ISBN 0-306-44867-X); Vaccine Adjuvants: PreparationMethods and Research Protocols (Volume 42 of Methods in MolecularMedicine series). ISBN: 1-59259-083-7. Ed. O'Hagan; Allison & Byars(1992) Res Immunol 143:519-25; Hariharan et al. (1995) Cancer Res55:3486-9; US-2007/014805; Suli et al. (2004) Vaccine 22(25-26):3464-9;WO95/11700; U.S. Pat. No. 6,080,725; WO2005/097181; WO2006/113373; Hanet al. (2005) Impact of Vitamin E on Immune Function and InfectiousDiseases in the Aged at Nutrition, Immune functions and HealthEuroConference, Paris, 9-10 Jun. 2005; U.S. Pat. No. 6,630,161; U.S.Pat. No. 5,057,540; WO96/33739; EP-A-0109942; and WO96/11711.Optionally, the ISCOMS may be devoid of additional detergent(WO00/07621).

A review of the development of saponin based adjuvants can be found inBarr et al. (1998) Advanced Drug Delivery Reviews 32:247-271 andSjolanderet et al. (1998) Advanced Drug Delivery Reviews 32:321-338.

D. Virosoines and Virus-Like Particles

Virosomes and virus-like particles (VLPs) can also be used as adjuvantsin the invention. These structures generally contain one or moreproteins from a virus optionally combined or formulated with aphospholipid. They are generally non-pathogenic, non-replicating andgenerally do not contain any of the native viral genome. The viralproteins may be recombinantly produced or isolated from whole viruses.These viral proteins suitable for use in virosomes or VLPs includeproteins derived from influenza virus (such as HA or NA), Hepatitis Bvirus (such as core or capsid proteins), Hepatitis E virus, measlesvirus, Sindbis virus, Rotavirus, Foot-and-Mouth Disease virus,Retrovirus, Norwalk virus, human Papilloma virus, HIV, RNA-phages,QB-phage (such as coat proteins), GA-phage, fr-phage, AP205 phage, andTy (such as retrotransposon Ty protein pl). VLPs are discussed furtherin Niikura et al. (2002) Virology 293:273-280; Lenz et al. (2001) JImmunol 166:5346-5355; Pinto et al. (2003) J Infect Dis 188:327-338;Gerber et al. (2001) J Virol 75:4752-4760; WO03/024480 and WO03/024481.Virosomes are discussed further in, for example, Gluck et al. (2002)Vaccine 20:B10-B16.

E. Bacterial or Microbial Derivatives

Adjuvants suitable for use in the invention include bacterial ormicrobial derivatives such as non-toxic derivatives of enterobacteriallipopolysaccharide (LPS), Lipid A derivatives, immunostimulatoryoligonucleotides and ADP-ribosylating toxins and detoxified derivativesthereof.

Non-toxic derivatives of LPS include monophosphoryl lipid A (MPL) and3-0-deacylated MPL (3dMPL). 3dMPL is a mixture of 3 de-O-acylatedmonophosphoryl lipid A with 4, 5 or 6 acylated chains. A preferred“small particle” form of 3 De-O-acylated monophosphoryl lipid A isdisclosed in EP-A-0689454. Such “small particles” of 3dMPL are smallenough to be sterile filtered through a 0.22 μm membrane (U.S. Pat. No.6,630,161). Other non-toxic LPS derivatives include monophosphoryl lipidA mimics, such as aminoalkyl glucosaminide phosphate derivatives e.g.RC-529 (Johnson et al. (1999) Bioorg Med Chem Lett 9:2273-2278; andEvans et al. (2003) Expert Rev Vaccines 2:219-229). Lipid A derivativesinclude derivatives of lipid A from Escherichia coli such as OM-174.OM-174 is described for example in Meraldi et al. (2003) Vaccine21:2485-2491 and Pajak et al. (2003) Vaccine 21:836-842.

Immunostimulatory oligonucleotides suitable for use as adjuvants in theinvention include nucleotide sequences containing a CpG motif (adinucleotide sequence containing an unmethylated cytosine linked by aphosphate bond to a guanosine). Double-stranded RNAs andoligonucleotides containing palindromic or poly(dG) sequences have alsobeen shown to be immunostimulatory.

The CpG's can include nucleotide modifications/analogs such asphosphorothioate modifications and can be double-stranded orsingle-stranded. Kandimalla et al. (2003) Nucleic Acids Research31:2393-2400, WO02/26757 and WO99/62923 disclose possible analogsubstitutions e.g. replacement of guanosine with2′-deoxy-7-deazaguanosine. The adjuvant effect of CpG oligonucleotidesis further discussed in Krieg (2003) Nature Medicine 9:831-835;McCluskie et al. (2002) FEMS Immunology and Medical Microbiology32:179-185; WO98/40100; U.S. Pat. No. 6,207,646; U.S. Pat. No. 6,239,116and U.S. Pat. No. 6,429,199.

The CpG sequence may be directed to TLR9, such as the motif GTCGTT orTTCGTT (Kandimalla et al. (2003) Biochemical Society Transactions 31(part 3):654-658). The CpG sequence may be specific for inducing a Th1immune response, such as a CpG-A ODN, or it may be more specific forinducing a B cell response, such a CpG-B ODN. CpG-A and CpG-B ODNs arediscussed in Blackwell et al. (2003) J Immunol 170:4061-4068; Krieg(2002) Trends Immunol 23:64-65; and WO01/95935. Preferably, the CpG is aCpG-A ODN.

Preferably, the CpG oligonucleotide is constructed so that the 5′ end isaccessible for receptor recognition. Optionally, two CpG oligonucleotidesequences may be attached at their 3′ ends to form “immunomers”. See,for example, Gluck et al. (2002) Vaccine 20:B10-B16; Kandimalla et al.(2003) BBRC 306:948-953; Bhagat et al. (2003) BBRC 300:853-861; andWO03/035836.

A useful CpG adjuvant is CpG7909, also known as ProMune™ (ColeyPharmaceutical Group, Inc.). Another is CpG1826. As an alternative, orin addition, to using CpG sequences, TpG sequences can be used(WO01/22972), and these oligonucleotides may be free from unmethylatedCpG motifs. The immunostimulatory oligonucleotide may bepyrimidine-rich. For example, it may comprise more than one consecutivethymidine nucleotide (e.g. TTTT, as disclosed in Pajak et al. (2003)Vaccine 21:836-842), and/or it may have a nucleotide compositionwith >25% thymidine (e.g. >35%, >40%, >50%, >60%, >80%, etc.). Forexample, it may comprise more than one consecutive cytosine nucleotide(e.g. CCCC, as disclosed in Pajak et al. (2003) Vaccine 21:836-842),and/or it may have a nucleotide composition with >25% cytosine(e.g. >35%, >40%, >50%, >60%, >80%, etc.). These oligonucleotides may befree from unmethylated CpG motifs. Immunostimulatory oligonucleotideswill typically comprise at least 20 nucleotides. They may comprise fewerthan 100 nucleotides.

A particularly useful adjuvant based around immunostimulatoryoligonucleotides is known as IC-31™ (Schellack et al. (2006) Vaccine24:5461-72). Thus an adjuvant used with the invention may comprise amixture of (i) an oligonucleotide (e.g. between 15-40 nucleotides)including at least one (and preferably multiple) Cp1 motifs (i.e. acytosine linked to an inosine to form a dinucleotide), and (ii) apolycationic polymer, such as an oligopeptide (e.g. between 5-20 aminoacids) including at least one (and preferably multiple) Lys-Arg-Lystripeptide sequence(s). The oligonucleotide may be a deoxynucleotidecomprising 26-mer sequence 5′-(IC)₁₃-3′. The polycationic polymer may bea peptide comprising 11-mer amino acid sequence KLKLLLLLKLK.

Bacterial ADP-ribosylating toxins and detoxified derivatives thereof maybe used as adjuvants in the invention. Preferably, the protein isderived from E. coli (E. coli heat labile enterotoxin “LT”), cholera(“CT”), or pertussis (“PT”). The use of detoxified ADP-ribosylatingtoxins as mucosal adjuvants is described in WO95/17211 and as parenteraladjuvants in WO98/42375. The toxin or toxoid is preferably in the formof a holotoxin, comprising both A and B subunits. Preferably, the Asubunit contains a detoxifying mutation; preferably the B subunit is notmutated. Preferably, the adjuvant is a detoxified LT mutant such asLT-K63, LT-R72, and LT-G192. The use of ADP-ribosylating toxins anddetoxified derivatives thereof, particularly LT-K63 and LT-R72, asadjuvants can be found in Beignon et al. (2002) Infect Immun70:3012-3019; Pizza et al. (2001) Vaccine 19:2534-2541; Pizza et al.(2000) Int J Med Microbiol 290:455-461; Scharton-Kersten et al. (2000)Infect Immun 68:5306-5313; Ryan et al. (1999) Infect Immun 67:6270-6280;Partidos et al. (1999) Immunol Lett 67:209-216; Peppoloni et al. (2003)Expert Rev Vaccines 2:285-293; and Pine et al. (2002) J Control Release85:263-270.

A useful CT mutant is or CT-E29H (Tebbey et al. (2000) Vaccine18:2723-34). Numerical reference for amino acid substitutions ispreferably based on the alignments of the A and B subunits ofADP-ribosylating toxins set forth in Domenighini et al. (1995) MolMicrobiol 15:1165-1167, specifically incorporated herein by reference inits entirety.

F. Human Immunomodulators

Human immunomodulators suitable for use as adjuvants in the inventioninclude cytokines, such as interleukins (e.g. IL-1, IL-2, IL-4, IL-5,IL-6, IL-7, IL-12 (WO99/40936), etc.) (WO99/44636), interferons (e.g.interferon-γ), macrophage colony stimulating factor, and tumor necrosisfactor. A preferred immunomodulator is IL-12.

G. Bioadhesives and Mucoadhesives

Bioadhesives and mucoadhesives may also be used as adjuvants in theinvention. Suitable bioadhesives include esterified hyaluronic acidmicrospheres (Singh et al. (2001) J Cont Release 70:267-276) ormucoadhesives such as cross-linked derivatives of poly(acrylic acid),polyvinyl alcohol, polyvinyl pyrollidone, polysaccharides andcarboxymethylcellulose. Chitosan and derivatives thereof may also beused as adjuvants in the invention (WO99/27960).

H. Microparticles

Microparticles may also be used as adjuvants in the invention.Microparticles (i.e. a particle of ˜100 nm to ˜150 μm in diameter, morepreferably ˜200 nm to ˜30 μm in diameter, and most preferably ˜500 nm to˜10 μm in diameter) formed from materials that are biodegradable andnon-toxic (e.g. a poly(α-hydroxy acid), a polyhydroxybutyric acid, apolyorthoester, a polyanhydride, a polycaprolactone, etc.), withpoly(lactide-co-glycolide) are preferred, optionally treated to have anegatively-charged surface (e.g. with SDS) or a positively-chargedsurface (e.g. with a cationic detergent, such as CTAB).

I. Liposomes (Chapters 13 & 14 of Vaccine Design . . . (1995) eds.Powell & Newman. ISBN. 030644867X Plenum.)

Examples of liposome formulations suitable for use as adjuvants aredescribed in U.S. Pat. No. 6,090,406; U.S. Pat. No. 5,916,588; andEP-A-0626169.

J. Polyoxyethylene Ether and Polyoxyethylene Ester Formulations

Adjuvants suitable for use in the invention include polyoxyethyleneethers and polyoxyethylene esters (WO99/52549). Such formulationsfurther include polyoxyethylene sorbitan ester surfactants incombination with an octoxynol (WO01/21207) as well as polyoxyethylenealkyl ethers or ester surfactants in combination with at least oneadditional non-ionic surfactant such as an octoxynol (WO01/21152).Preferred polyoxyethylene ethers are selected from the following group:polyoxyethylene-9-lauryl ether (laureth 9), polyoxyethylene-9-steorylether, polyoxytheylene-8-steoryl ether, polyoxyethylene-4-lauryl ether,polyoxyethylene-35-lauryl ether, and polyoxyethylene-23-lauryl ether.

K Phosphazenes

A phosphazene, such as poly[di(carboxylatophenoxy)phosphazene] (“PCPP”)as described, for example, in Andrianov et al. (1998) Biomaterials19:109-115 and Payne et al. (1998) Adv Drug Delivery Review 31:185-196,may be used.

L. Muramyl Peptides

Examples of muramyl peptides suitable for use as adjuvants in theinvention include N-acetyl-muramyl-L-thrconyl-D-isoglutamine (thr-MDP),N-acetyl-normuramyl-L-alanyl-D-isoglutamine (nor-MDP), andN-acetylmuramyl-L-alanyl-D-isoglutaminyl-L-alanine-2-(1′-2′-dipalmitoyl-sn-glycero-3-hydroxyphosphoryloxy)-ethylamineMTP-PE).

M. Imidazoquinolone Compounds.

Examples of imidazoquinolone compounds suitable for use adjuvants in theinvention include Imiquimod (“R-837”) (U.S. Pat. No. 4,680,338; U.S.Pat. No. 4,988,815), Resiquimod (“R-848”) (WO92/15582), and theiranalogs; and salts thereof (e.g. the hydrochloride salts). Furtherdetails about immunostimulatory imidazoquinolines can be found inStanley (2002) Clin Exp Dermatol 27:571-577; Wu et al. (2004) AntiviralRes. 64(2):79-83; Vasilakos et al. (2000) Cell Immunol. 204(1):64-74;U.S. Pat. Nos. 4,689,338, 4,929,624, 5,238,944, 5,266,575, 5,268,376,5,346,905, 5,352,784, 5,389,640, 5,395,937, 5,482,936, 5,494,916,5,525,612, 6,083,505, 6,440,992, 6,627,640, 6,656,938, 6,660,735,6,660,747, 6,664,260, 6,664,264, 6,664,265, 6,667,312, 6,670,372,6,677,347, 6,677,348, 6,677,349, 6,683,088, 6,703,402, 6,743,920,6,800,624, 6,809,203, 6,888,000 and 6,924,293; and Jones (2003) CurrOpin Investig Drugs 4:214-218.

N. Substituted Ureas

Substituted ureas useful as adjuvants include compounds of formula I, IIor III, or salts thereof:

as defined in WO03/011223, such as ‘ER 803058’, ‘ER 803732’, ‘ER804053’, ER 804058’, ‘ER 804059’, ‘ER 804442’, ‘ER 804680’, ‘ER 804764’,ER 803022 or ‘ER 804057’ e.g.:

O. Further Adjuvants

Further adjuvants that may be used with the invention include:

-   -   An aminoalkyl glucosaminide phosphate derivative, such as RC-529        (Johnson et al. (1999) Bioorg Med Chem Lett 9:2273-2278; Evans        et al. (2003) Expert Rev Vaccines 2:219-229)    -   A thiosemicarbazone compound, such as those disclosed in        WO2004/060308. Methods of formulating, manufacturing, and        screening for active compounds are also described in Bhagat et        al. (2003) BBRC 300:853-861. The thiosemicarbazones are        particularly effective in the stimulation of human peripheral        blood mononuclear cells for the production of cytokines, such as        TNF-α.    -   A tryptanthrin compound, such as those disclosed in        WO2004/064759. Methods of formulating, manufacturing, and        screening for active compounds are also described in        WO03/035836. The thiosemicarbazones are particularly effective        in the stimulation of human peripheral blood mononuclear cells        for the production of cytokines, such as TNF-α.    -   A nucleoside analog, such as: (a) Isatorabine (ANA-245;        7-thia-8-oxoguanosine):

-   -   and prodrugs thereof; (b) ANA975; (c) ANA-025-1; (d) ANA380; (e)        the compounds disclosed in U.S. Pat. No. 6,924,271,        US2005/0070556 and U.S. Pat. No. 5,658,731, oxoribine        (7-allyl-8-oxoguanosine) (U.S. Pat. No. 5,011,828).    -   Compounds disclosed in WO2004/87153, including: Acylpiperazine        compounds, Indoledione compounds, Tetrahydraisoquinoline (THIQ)        compounds, Benzocyclodione compounds, Aminoazavinyl compounds,        Aminobenzimidazole quinolinone (ABIQ) compounds (U.S. Pat. No.        6,605,617, WO02/18383), Hydrapthalamide compounds, Benzophenone        compounds, Isoxazole compounds, Sterol compounds, Quinazilinone        compounds, Pyrrole compounds (WO2004/018455), Anthraquinone        compounds, Quinoxaline compounds, Triazine compounds,        Pyrazalopyrimidine compounds, and Benzazole compounds        (WO03/082272).    -   Compounds containing lipids linked to a phosphate-containing        acyclic backbone, such as the TLR4 antagonist E5564 (Wong et        al. (2003) J Clin Pharmacol 43(7):735-42; US2005/0215517).    -   A polyoxidonium polymer (Dyakonova et al. (2004) Int        Immunopharmacol 4(13):1615-23; FR-2859633) or other N-oxidized        polyethylene-piperazine derivative.    -   Methyl inosine 5′-monophosphate (“MIMP”) (Signorelli &        Hadden (2003) Int Immunopharmacol 3(8): 1177-86).    -   A polyhydroxlated pyrrolizidine compound (WO2004/064715), such        as one having formula:

-   -   where R is selected from the group comprising hydrogen, straight        or branched, unsubstituted or substituted, saturated or        unsaturated acyl, alkyl (e.g. cycloalkyl), alkenyl, alkynyl and        aryl groups, or a pharmaceutically acceptable salt or derivative        thereof. Examples include, but are not limited to: casuarine,        casuarine-6-α-D-glucopyranose, 3-epi-casuarine, 7-epi-casuarine,        3,7-diepi-casuarine, etc.    -   A CD1d ligand, such as an α-glycosylceramide (De Libero et al,        Nature Reviews Immunology, 2005, 5: 485-496; U.S. Pat. No.        5,936,076; Oki et al. J. Clin. Investig., 113: 1631-1640 ;        US2005/0192248; Yang et al, Angew. Chem. Int. Ed., 2004, 43:        3818-3822; WO2005/102049; Goff et al, J. Am. Chem., Soc., 2004,        126: 13602-13603; WO03/105769) e.g. α-galactosylceramide),        phytosphingosine-containing α-glycosylceramides, OCH, KRN7000        [(2S,3S,4R)-1-O-(α-D-galactopyranosyl)-2-(N-hexacosanoylamino)-1,3,4-octadecanetriol]        CRONY-101, 3″-O-sulfo-galactosylceramide, etc.    -   A gamma inulin (Cooper (1995) Pharm Biotechnol 6:559-80) or        derivative thereof, such as algammulin.

Adjuvant Combinations

The invention may also comprise combinations of one or more of theadjuvants identified above. For example, the following adjuvantcompositions may be used in the invention: (1) a saponin and anoil-in-water emulsion (WO99/11241); (2) a saponin (e.g. QS21) +anon-toxic LPS derivative (e.g. 3dMPL) (WO94/00153); (3) a saponin (e.g.QS21)+a non-toxic LPS derivative (e.g. 3dMPL)+a cholesterol; (4) asaponin (e.g. QS21)+3dMPL+IL-12 (optionally+a sterol) (WO98/57659); (5)combinations of 3dMPL with, for example, QS21 and/or oil-in-wateremulsions (European patent applications 0835318, 0735898 and 0761231);(6) SAF, containing 10% squalane, 0.4% Tween 80™, 5% pluronic-blockpolymer L121, and thr-MDP, either microfluidized into a submicronemulsion or vortexed to generate a larger particle size emulsion. (7)Ribi™ adjuvant system (RAS), (Ribi Immunochem) containing 2% squalene,0.2% Tween 80, and one or more bacterial cell wall components from thegroup consisting of monophosphorylipid A (MPL), trehalose dimycolate(TDM), and cell wall skeleton (CWS), preferably MPL+CWS (Detox™); and(8) one or more mineral salts (such as an aluminum salt)+a non-toxicderivative of LPS (such as 3dMPL). In some embodiments a combination ofa toxin (e.g. LTK63) and an immunostimulatory oligonucleotide (e.g. CpG)is used. In some embodiments, a combination of an emulsion (e.g.montanide) and an immunostimulatory oligonucleotide (e.g. CpG) is used.

Other substances that act as immunostimulating agents are disclosed inchapter 7 of Vaccine Design, (1995) eds. Powell & Newman. ISBN:030644867X. Plenum.

The use of an aluminium hydroxide and/or aluminium phosphate adjuvant isparticularly preferred, and antigens are generally adsorbed to thesesalts. Calcium phosphate is another preferred adjuvant. Other preferredadjuvant combinations include combinations of Th1 and Th2 adjuvants suchas CpG & alum or resiquimod & alum. A combination of aluminium phosphateand 3dMPL may be used.

To improve thermal stability, a composition may include a temperatureprotective agent. This component may be particularly useful inadjuvanted compositions (particularly those containing a mineraladjuvant, such as an aluminium salt). As described in WO2006/110603, aliquid temperature protective agent may be added to an aqueous vaccinecomposition to lower its freezing point e.g. to reduce the freezingpoint to below 0° C. Thus the composition can be stored below 0° C., butabove its freezing point, to inhibit thermal breakdown. The temperatureprotective agent also permits freezing of the composition whileprotecting mineral salt adjuvants against agglomeration or sedimentationafter freezing and thawing, and may also protect the composition atelevated temperatures e.g. above 40° C. A starting aqueous vaccine andthe liquid temperature protective agent may be mixed such that theliquid temperature protective agent forms from 1-80% by volume of thefinal mixture. Suitable temperature protective agents should be safe forhuman administration, readily miscible/soluble in water, and should notdamage other components (e.g. antigen and adjuvant) in the composition.Examples include glycerin, propylene glycol, and/or polyethylene glycol(PEG). Suitable PEGs may have an average molecular weight ranging from200-20,000 Da. In a preferred embodiment, the polyethylene glycol canhave an average molecular weight of about 300 Da (PEG-300′).

The invention provides an immunogenic composition comprising: (i) one ormore proteins of the invention; and (ii) a temperature protective agent.This composition may be formed by mixing (i) an aqueous compositioncomprising one or more proteins of the invention, with (ii) atemperature protective agent. The mixture may then be stored e.g. below0° C., from 0-20° C., from 20-35° C., from 35-55° C., or higher. It maybe stored in liquid or frozen form. The mixture may be lyophilised. Thecomposition may alternatively be formed by mixing (i) a driedcomposition comprising one or more proteins of the invention, with (ii)a liquid composition comprising the temperature protective agent. Thuscomponent (ii) can be used to reconstitute component (i).

The compositions of the invention may elicit either or both of a cellmediated immune response and a humoral immune response. This immuneresponse will preferably induce long lasting (e.g. neutralising)antibodies and a cell mediated immunity that can quickly respond uponexposure to chlamydia.

Two types of T cells, CD4 and CD8 cells, are generally thought necessaryto initiate and/or enhance cell mediated immunity and humoral immunity.CD8 T cells can express a CD8 co-receptor and are commonly referred toas Cytotoxic T lymphocytes (CTLs). CD8 T cells are able to recognized orinteract with antigens displayed on MHC Class I molecules.

CD4 T cells can express a CD4 co-receptor and are commonly referred toas T helper cells. CD4 T cells are able to recognize antigenic peptidesbound to MHC class II molecules. Upon interaction with a MHC class IImolecule, the CD4 cells can secrete factors such as cytokines. Thesesecreted cytokines can activate B cells, cytotoxic T cells, macrophages,and other cells that participate in an immune response. Helper T cellsor CD4+ cells can be further divided into two functionally distinctsubsets: TH1 phenotype and TH2 phenotypes which differ in their cytokineand effector function.

Activated TH1 cells enhance cellular immunity (including an increase inantigen-specific CTL production) and are therefore of particular valuein responding to intracellular infections. Activated TH1 cells maysecrete one or more of IL-2, IFNγ, and TNF-β. A TH1 immune response mayresult in local inflammatory reactions by activating macrophages, NK(natural killer) cells, and CD8 cytotoxic T cells (CTLs). A TH1 immuneresponse may also act to expand the immune response by stimulatinggrowth of B and T cells with IL-12. TH1 stimulated B cells may secreteIgG2a.

Activated TH2 cells enhance antibody production and are therefore ofvalue in responding to extracellular infections. Activated TH2 cells maysecrete one or more of IL-4, IL-5, IL-6, and IL-10. A TH2 immuneresponse may result in the production of IgGI, IgE, IgA and memory Bcells for future protection.

An enhanced immune response may include one or more of an enhanced TH1immune response and a TH2 immune response.

A TH1 immune response may include one or more of an increase in CTLs, anincrease in one or more of the cytokines associated with a TH1 immuneresponse (such as IL-2, 1FNγ, and TNF-β), an increase in activatedmacrophages, an increase in NK activity, or an increase in theproduction of IgG2a. Preferably, the enhanced TH1 immune response willinclude an increase in IgG2a production.

A TH1 immune response may be elicited using a TH1 adjuvant. A TH1adjuvant will generally elicit increased levels of IgG2a productionrelative to immunization of the antigen without adjuvant. TH1 adjuvantssuitable for use in the invention may include for example saponinformulations, virosomes and virus like particles, non-toxic derivativesof enterobacterial lipopolysaccharide (LPS), immunostimulatoryoligonucleotides. Immunostimulatory oligonucleotides, such asoligonucleotides containing a CpG motif, are preferred TH1 adjuvants foruse in the invention.

A TH2 immune response may include one or more of an increase in one ormore of the cytokines associated with a TH2 immune response (such asIL-4, IL-5, IL-6 and IL-10), or an increase in the production of IgG1,IgE, IgA and memory B cells. Preferably, the enhanced TH2 immune resonsewill include an increase in IgG1 production.

A TH2 immune response may be elicited using a TH2 adjuvant. A TH2adjuvant will generally elicit increased levels of IgG1 productionrelative to immunization of the antigen without adjuvant. TH2 adjuvantssuitable for use in the invention include, for example, mineralcontaining compositions, oil-emulsions, and ADP-ribosylating toxins anddetoxified derivatives thereof. Mineral containing compositions, such asaluminium salts are preferred TH2 adjuvants for use in the invention.

Preferably, the invention includes a composition comprising acombination of a TH1 adjuvant and a TH2 adjuvant. Preferably, such acomposition elicits an enhanced TH1 and an enhanced TH2 response, i.e.,an increase in the production of both IgG1 and IgG2a production relativeto immunization without an adjuvant. Still more preferably, thecomposition comprising a combination of a TH1 and a TH2 adjuvant elicitsan increased TH1 and/or an increased TH2 immune response relative toimmunization with a single adjuvant (i.e., relative to immunization witha TH1 adjuvant alone or immunization with a TH2 adjuvant alone).

The immune response may be one or both of a TH1 immune response and aTH2 response. Preferably, immune response provides for one or both of anenhanced TH1 response and an enhanced TH2 response. Preferably, theimmune response includes an increase in the production of IgG1 and/orIgG2 and/or IgGA.

The invention is preferably used to elicit systemic and/or mucosalimmunity. The enhanced immune response may be one or both of a systemicand a mucosal immune response. Preferably, the immune response providesfor one or both of an enhanced systemic and an enhanced mucosal immuneresponse. Preferably the mucosal immune response is a TH2 immuneresponse. Preferably, the mucosal immune response includes an increasein the production of IgA.

Methods of Treatment, and Administration of the Vaccine

The invention also provides a method for raising an immune response in amammal comprising the step of administering an effective amount of aprotein, antibody, nucleic acid, vector, host cell or composition of theinvention. The immune response is preferably protective and preferablyinvolves antibodies and/or cell-mediated immunity. The method may raisea booster response.

The invention also provides a protein or combination, as defined above,for use as a medicament e.g. for use in raising an immune response in amammal.

The invention also provides the use of a protein or combination of theinvention in the manufacture of a medicament for raising an immuneresponse in a mammal. By raising an immune response in the mammal bythese uses and methods, the mammal can be protected against Chlamydiainfection. More particularly, the mammal may be protected againstChlamydia trachomatis. The invention is effective against Chlamydia ofvarious different serotypes, but can be particularly useful inprotecting against disease resulting from Chlamydia infection by strainsin serovar D.

Thus, according to a further aspect, the invention also provides anucleic acid, protein, antibody, vector or host cell according to theinvention for use as a medicament (e.g. a vaccine) or a diagnosticreagent. In one embodiment, the protein, nucleic acid or antibody isused for treatment, prevention or diagnosis of Chlamydia infection(preferably C. trachomatis) in a mammal. The invention also provides amethod of treating, preventing of diagnosing Chlamydia infection(preferably, C. trachomatis infection) in a patient (preferably amammal), comprising administering a therapeutically effective amount ofa nucleic acid, protein or antibody of the invention.

Preferably, the nucleic acid, protein or antibody according to theinvention is for treatment or prevention of Chlamydia infection or anassociated condition (e.g. trachoma, blindness, cervicitis, pelvicinflammatory disease, infertility, ectopic pregnancy, chronic pelvicpain, salpingitis, urethritis, epididymitis, infant pneumonia, cervicalsquamous cell carcinoma, etc.), preferably, C. trachomatis infection.The immunogenic composition may additionally or alternatively beeffective against C. pneumoniae.

The mammal is preferably a human. Where the vaccine is for prophylacticuse, the human is preferably a child (e.g. a toddler or infant) or ateenager; where the vaccine is for therapeutic use, the human ispreferably a teenager or an adult. A vaccine intended for children mayalso be administered to adults e.g. to assess safety, dosage,immunogenicity, etc. Thus a human patient may be less than 1 year old,1-5 years old, 5-15 years old, 15-55 years old, or at least 55 yearsold. Preferred patients for receiving the vaccines are people goingthrough purberty, teenagers, sexually active people, the elderly (e.g.≧50 years old, ≧60 years old, and preferably ≧65 years), the young (e.g.≦5 years old), hospitalised patients, healthcare workers, armed serviceand military personnel, pregnant women, the chronically ill, orimmunodeficient patients. The vaccines are not suitable solely for thesegroups, however, and may be used more generally in a population.

Vaccines produced by the invention may be administered to patients atsubstantially the same time as (e.g during the same medical consultationor visit to a healthcare professional or vaccination centre) othervaccines e.g. at substantially the same time as a human papillomavirusvaccine such as Cervarix™ or Gardasil™; a tetanus, diphtheria andacellular pertussis vaccine such as TDaP, DTaP or Boostrix™; a rubellavaccine such as MMR; or a tubercolosis vaccine such as the BCG. Examplesof other vaccines that the vaccine produced by the invention may beadministered at substantially the same time as are a measles vaccine, amumps vaccine, a varicella vaccine, a MMRV vaccine, a diphtheriavaccine, a tetanus vaccine, a pertussis vaccine, a DTP vaccine, aconjugated H. influenzae type b vaccine, an inactivated poliovirusvaccine, a hepatitis B virus vaccine, a meningococcal conjugate vaccine(such as a tetravalent A-C-W135-Y vaccine), a respiratory syncytialvirus vaccine, etc.

In a preferred embodiment, the protein of the invention is used toelicit antibodies that are capable of neutralising the activity of thewild type Chlamydia protein, for example, of one or more of wild-typeChlamydia CT733, CT153, CT601, CT279, CT443, CT372, CT456, CT381, CT255,CT341, CT716, CT745, CT387, CT812, CT869, CT166, CT175, CT163, CT214,CT721, CT127, CT043, CT600 and/or CT823 for example, of one or more ofwild-type Chlamydia CT733, CT153, CT601, CT279, CT443, CT372, CT456and/or CT381. Neutralizing antibodies may be used as a vaccine capableof neutralising the activity of a native Chlamydia protein expressed byinfectious EB. In one embodiment, the protein of the invention is usedto elicit antibodies that are capable of neutralising Chlamydiainfectivity and/or virulence. Thus, the invention also provides theantibodies of the invention for neutralising wild-type Chlamydiaproteins and/or Chlamydia infectivity and/or virulence.

The invention also provides the use of a nucleic acid, protein, orantibody of the invention in the manufacture of: (i) a medicament fortreating or preventing bacterial infection; (ii) a diagnostic reagentfor detecting the presence of bacteria or of antibodies raised againstbacteria; and/or (iii) a reagent which can raise antibodies againstbacteria. Said bacteria is preferably a Chlamydia, e.g. Chlamydiatrachomatis or Chlamydia pneumoniae, but is preferably Chlamydiatrachomatis.

Also provided is a method for diagnosing Chlamydia infection,comprising:

-   -   (a) raising an antibody against a protein of the invention;    -   (b) contacting the antibody of step (a) with a biological sample        suspected of being infected with Chlamydia under conditions        suitable for the formation of antibody-antigen complexes; and    -   (c) detecting said complexes, wherein detection of said complex        is indicative of Chlamydia infection.

Also provided is a method for diagnosing Chlamydia infection,comprising: (a) contacting an antibody which was raised against aprotein of the invention with a biological sample suspected of beinginfected with Chlamydia under conditions suitable for the formation ofantibody-antigen complexes; and (b) detecting said complexes, whereindetection of said complex is indicative of Chlamydia infection.

Proteins of the invention can be used in immunoassays to detect antibodylevels (or, conversely, antibodies of the invention can be used todetect protein levels). Immunoassays based on well defined, recombinantantigens can be developed to replace invasive diagnostics methods.Antibodies to proteins within biological samples, including for example,blood or serum samples, can be detected. Design of the immunoassays issubject to a great deal of variation, and a variety of these are knownin the art. Protocols for the immunoassay may be based, for example,upon competition, or direct reaction, or sandwich type assays. Protocolsmay also, for example, use solid supports, or may be byimmunoprecipitation. Most assays involve the use of labeled antibody orpolypeptide; the labels may be, for example, fluorescent,chemiluminescent, radioactive, or dye molecules. Assays which amplifythe signals from the probe are also known; examples of which are assayswhich utilize biotin and avidin, and enzyme-labeled and mediatedimmunoassays, such as ELISA assays.

Kits suitable for immunodiagnosis and containing the appropriate labeledreagents are constructed by packaging the appropriate materials,including the compositions of the invention, in suitable containers,along with the remaining reagents and materials (for example, suitablebuffers, salt solutions, etc.) required for the conduct of the assay, aswell as suitable set of assay instructions.

Testing Efficacy of Compositions

The efficacy of the immunogenic compositions of the present inventioncan be evaluated in in vitro and in vivo animal models prior to host,e.g., human, administration. For example, in vitro neutralization byPeterson et al (1988) is suitable for testing vaccine compositionsdirected toward Chlamydia trachomatis.

One way of checking efficacy of therapeutic treatment involvesmonitoring C. trachomatis infection after administration of thecompositions of the invention. One way of checking efficacy ofprophylactic treatment involves monitoring immune responses bothsystemically (such as monitoring the level of IgG1 and IgG2a production)and mucosally (such as monitoring the level of IgA production) againstthe Chlamydia trachomatis antigens in the compositions of the inventionafter administration of the composition. Typically, serum Chlamydiaspecific antibody responses are determined post-immunisation butpre-challenge whereas mucosal Chlamydia specific antibody body responsesare determined post-immunisation and post-challenge.

One example of such an in vitro test is described as follows.Hyper-immune antisera is diluted in PBS containing 5% guinea pig serum,as a complement source. Chlamydia trachomatis (10⁴ IFU; inclusionforming units) are added to the antisera dilutions. The antigen-antibodymixtures are incubated at 37° C. for 45 minutes and inoculated intoduplicate confluent Hep-2 or HeLa cell monolayers contained in glassvials (e.g., 15 by 45 mm), which have been washed twice with PBS priorto inoculation. The monolayer cells are infected by centrifugation at1000×g for 1 hour followed by stationary incubation at 37° C. for 1hour. Infected monolayers are incubated for 48 or 72 hours, fixed andstained with Chlamydia specific antibody, such as anti-MOMP.Inclusion-bearing cells are counted in ten fields at a magnification of200×. Neutralization titer is assigned on the dilution that gives 50%inhibition as compared to control monolayers/IFU.

Another way of assessing the immunogenicity of the compositions of thepresent invention is to express the proteins recombinantly for screeningpatient sera or mucosal secretions by immunoblot and/or microarrays. Apositive reaction between the protein and the patient sample indicatesthat the patient has mounted an immune response to the protein inquestion. This method may also be used to identify immunodominantantigens and/or epitopes within antigens.

The efficacy of vaccine compositions can also be determined in vivo bychallenging animal models of Chlamydia trachomatis infection, e.g.,guinea pigs or mice, with the vaccine compositions. For example, in vivovaccine composition challenge studies in the guinea pig model ofChlamydia trachomatis infection can be performed. A description of oneexample of this type of approach follows. Female guinea pigs weighing450-500 g are housed in an environmentally controlled room with a 12hour light-dark cycle and immunized with vaccine compositions via avariety of immunization routes. Post-vaccination, guinea pigs areinfected in the genital tract with the agent of guinea pig inclusionconjunctivitis (GPIC), which has been grown in HeLa or McCoy cells (Ranket al. (1988)). Each animal receives approximately 1.4×10⁷ inclusionforming units (IFU) contained in 0.05 ml of sucrose-phosphate-glutamatebuffer, pH 7.4 (Schacter, 1980). The course of infection monitored bydetermining the percentage of inclusion-bearing cells by indirectimmunofluorescence with GPIC specific antisera, or by Giemsa-stainedsmear from a scraping from the genital tract (Rank et al 1988). Antibodytiters in the serum is determined by an enzyme-linked immunosorbentassay.

Alternatively, in vivo vaccine compositions challenge studies can beperformed in the murine model of Chlamydia trachomatis (Morrison et al1995). A description of one example of this type of approach is asfollows. Female mice 7 to 12 weeks of age receive 2.5 mg of depo-proverasubcutaneously at 10 and 3 days before vaginal infection.Post-vaccination, mice are infected in the genital tract with 1,500inclusion-forming units of Chlamydia trachomatis contained in 5 ml ofsucrose-phosphate-glutamate buffer, pH 7.4. The course of infection ismonitored by determining the percentage of inclusion-bearing cells byindirect immunofluorescence with Chlamydia trachomatis specificantisera, or by a Giemsa-stained smear from a scraping from the genitaltract of an infected mouse. The presence of antibody titers in the serumof a mouse is determined by an enzyme-linked immunosorbent assay.

Nucleic Acid Immunisation

The immunogenic compositions described above include Chlamydia antigens.In all cases, however, the polypeptide antigens can be replaced bynucleic acids (typically DNA) encoding those polypeptides, to givecompositions, methods and uses based on nucleic acid immunisation.Nucleic acid immunisation is now a developed field (e.g. see Donnelly etal. (1997) Annu Rev Immunol 15:617-648; Strugnell et al. (1997) ImmunolCell Blot 75(4):364-369; Cui (2005) Adv Genet 54:257-89; Robinson &Torres (1997) Seminars in Immunol 9:271-283; Brunham et al. (2000) JInfect Dis 181 Suppl 3:S538-43; Svanholm et al. (2000) Scand J Immunol51(4):345-53; DNA Vaccination—Genetic Vaccination (1998) eds. Koprowskiet al. (ISBN 3540633928); Gene Vaccination: Theory and Practice (1998)ed. Raz (ISBN 3540644288), etc.).

The nucleic acid encoding the immunogen is expressed in vivo afterdelivery to a patient and the expressed immunogen then stimulates theimmune system. The active ingredient will typically take the form of anucleic acid vector comprising: (i) a promoter; (ii) a sequence encodingthe immunogen, operably linked to the promoter; and optionally (iii) aselectable marker. Preferred vectors may further comprise (iv) an originof replication; and (v) a transcription terminator downstream of andoperably linked to (ii). In general, (i) & (v) will be eukaryotic and(iii) & (iv) will be prokaryotic.

Preferred promoters are viral promoters e.g. from cytomegalovirus (CMV).The vector may also include transcriptional regulatory sequences (e.g.enhancers) in addition to the promoter and which interact functionallywith the promoter. Preferred vectors include the immediate-early CMVenhancer/promoter, and more preferred vectors also include CMV intron A.The promoter is operably linked to a downstream sequence encoding animmunogen, such that expression of the immunogen-encoding sequence isunder the promoter's control.

Where a marker is used, it preferably functions in a microbial host(e.g. in a prokaryote, in a bacteria, in a yeast). The marker ispreferably a prokaryotic selectable marker (e.g. transcribed under thecontrol of a prokaryotic promoter). For convenience, typical markers areantibiotic resistance genes.

The vector of the invention is preferably an autonomously replicatingepisomal or extrachromosomal vector, such as a plasmid.

The vector of the invention preferably comprises an origin ofreplication. It is preferred that the origin of replication is active inprokaryotes but not in eukaryotes.

Preferred vectors thus include a prokaryotic marker for selection of thevector, a prokaryotic origin of replication, but a eukaryotic promoterfor driving transcription of the immunogen-encoding sequence. Thevectors will therefore (a) be amplified and selected in prokaryotichosts without polypeptide expression, but (b) be expressed in eukaryotichosts without being amplified. This arrangement is ideal for nucleicacid immunization vectors.

The vector of the invention may comprise a eukaryotic transcriptionalterminator sequence downstream of the coding sequence. This can enhancetranscription levels. Where the coding sequence does not have its own,the vector of the invention preferably comprises a polyadenylationsequence. A preferred polyadenylation sequence is from bovine growthhormone.

The vector of the invention may comprise a multiple cloning site.

In addition to sequences encoding the immunogen and a marker, the vectormay comprise a second eukaryotic coding sequence. The vector may alsocomprise an IRES upstream of said second sequence in order to permittranslation of a second eukaryotic polypeptide from the same transcriptas the immunogen. Alternatively, the immunogen-coding sequence may bedownstream of an IRES.

The vector of the invention may comprise unmethylated CpG motifs e.g.unmethylated DNA sequences which have in common a cytosine preceding aguanosine, flanked by two 5′ purines and two 3′ pyrimidines. In theirunmethylated form these DNA motifs have been demonstrated to be potentstimulators of several types of immune cell.

Vectors may be delivered in a targeted way. Receptor-mediated DNAdelivery techniques are described in, for example, Findeis et al.,Trends Biotechnol. (1993) 11:202; Chiou et al. (1994) Gene Therapeutics:Methods And Applications Of Direct Gene Transfer. ed. Wolff; Wu et al.,J. Biol. Chem. (1988) 263:621; Wu et J. Biol. Chem. (1994) 269:542;Zenke et al., Proc. Natl. Acad. Sci. (USA) (1990) 87:3655; and Wu etal., J. Biol. Chem. (1991) 266:338.

Therapeutic compositions containing a nucleic acid are administered in arange of about 100 ng to about 200 mg of DNA for local administration ina gene therapy protocol. Concentration ranges of about 500 ng to about50 mg, about 1 μg to about 2 mg, about 5 μg to about 500 μg, and about20 μg to about 100 μg of DNA can also be used during a gene therapyprotocol. Factors such as method of action (e.g. for enhancing orinhibiting levels of the encoded gene product) and efficacy oftransformation and expression are considerations which will affect thedosage required for ultimate efficacy. Where greater expression isdesired over a larger area of tissue, larger amounts of vector or thesame amounts re-administered in a successive protocol ofadministrations, or several administrations to different adjacent orclose tissue portions may be required to effect a positive therapeuticoutcome. In all cases, routine experimentation in clinical trials willdetermine specific ranges for optimal therapeutic effect.

Vectors can be delivered using gene delivery vehicles. The gene deliveryvehicle can be of viral or non-viral origin (see generally Jolly, CancerGene Therapy (1994) 1:51; Kimura, Human Gene Therapy (1994) 5:845;Connelly, Human Gene Therapy (1995) 1:185; and Kaplitt, Nature Genetics(1994) 6:148).

Viral-based vectors for delivery of a desired nucleic acid andexpression in a desired cell are well known in the art. Exemplaryviral-based vehicles include, but are not limited to, recombinantretroviruses (e.g. WO 90/07936; WO 94/03622; WO 93/25698; WO 93/25234;U.S. Pat. No. 5,219,740; WO 93/11230; WO 93/10218; U.S. Pat. No.4,777,127; GB Patent No. 2,200,651; EP-A-0345242; and WO 91/02805),alphavirus-based vectors (e.g. Sindbis virus vectors, Semliki forestvirus (ATCC VR-67; ATCC VR-1247), Ross River virus (ATCC VR-373; ATCCVR-1246) and Venezuelan equine encephalitis virus (ATCC VR-923; ATCCVR-1250; ATCC VR 1249; ATCC VR-532); hybrids or chimeras of theseviruses may also be used), poxvirus vectors (e.g. vaccinia, fowlpox,canarypox, modified vaccinia Ankara, etc.), adenovirus vectors, andadeno-associated virus (AAV) vectors (e.g. see WO 90/07936; WO 94/03622;WO 93/25698; WO 93/25234; U.S. Pat. No. 5,219,740; WO 93/11230; WO93/10218; U.S. Pat. No. 4,777,127; GB Patent No. 2,200,651;EP-A-0345242; WO 91/02805; WO 94/12649; WO 93/03769; WO 93/19191; WO94/28938; WO 95/11984; and WO 95/00655). Administration of DNA linked tokilled adenovirus (Curiel, Hum. Gene Ther. (1992) 3:147) can also beemployed.

Non-viral delivery vehicles and methods can also be employed, including,but not limited to, polycationic condensed DNA linked or unlinked tokilled adenovirus alone (e.g. De Libero et al, Nature ReviewsImmunology, 2005, 5: 485-496), ligand-linked DNA (Wu, J. Biol. Chem.(1989) 264:16985), eukaryotic cell delivery vehicles cells (U.S. Pat.No. 5,814,482; WO 95/07994; WO 96/17072; WO 95/30763; and WO 97/42338)and nucleic charge neutralization or fusion with cell membranes. NakedDNA can also be employed. Exemplary naked DNA introduction methods aredescribed in WO 90/11092 and U.S. Pat. No. 5,580,859. Liposomes (e.g.immunoliposomes) that can act as gene delivery vehicles are described inU.S. Pat. No. 5,422,120; WO 95/13796; WO 94/23697; WO 91/14445; andEP-0524968. Additional approaches are described in Philip, Mol. CellBiol. (1994) 14:2411 and Woffend in, Proc. Natl. Acad. Sci. (1994)91:11581.

Further non-viral delivery suitable for use includes mechanical deliverysystems such as the approach described in Donnelly et al. (1997) AnnuRev Immunol 15:617-648. Moreover, the coding sequence and the product ofexpression of such can be delivered through deposition ofphotopolymerized hydrogel materials or use of ionizing radiation (e.g.U.S. Pat. No. 5,206,152 and WO 92/11033). Other conventional methods forgene delivery that can be used for delivery of the coding sequenceinclude, for example, use of hand-held gene transfer particle gun (U.S.Pat. No. 5,149,655) or use of ionizing radiation for activatingtransferred genes (Strugnell et al. (1997) Immunol Cell Biol75(4):364-369 and Cui (2005) Adv Genet 54:257-89).

Delivery DNA using PLG {poly(lactide-co-glycolide)} microparticles is aparticularly preferred method e.g. by adsorption to the microparticles,which are optionally treated to have a negatively-charged surface (e.g.treated with SDS) or a positively-charged surface (e.g. treated with acationic detergent, such as CTAB).

Antibody Immunisation

The antibodies of the invention may be used, for example, forneutralising the activity of the wild-type Chlamydia protein. Antibodiesagainst Chlamydia antigens can be used for passive immunisation (Brandtet al. (2006) J Antimicrob Chemother. 58(6):1291-4. Epub 2006 Oct. 26).Thus the invention provides the use of antibodies of the invention intherapy. The invention also provides the use of such antibodies in themanufacture of a medicament. The invention also provides a method fortreating a mammal comprising the step of administering an effectiveamount of an antibody of the invention. As described above forimmunogenic compositions, these methods and uses allow a mammal to beprotected against Chlamydia infection.

Processes

According to further aspects, the invention provides various processes.

A process for producing a protein of the invention is provided,comprising the step of culturing a host cell of the invention underconditions which induce protein expression.

A process for producing protein or nucleic acid of the invention isprovided, wherein the protein or nucleic acid is synthesised in part orin whole using chemical means.

A process for detecting Chlamydia (preferably C. trachomatis) in abiological sample is also provided, comprising the step of contacting anucleic acid according to the invention with the biological sample underhybridising conditions. The process may involve nucleic acidamplification (e.g. PCR, SDA, SSSR, LCR, TMA etc.) or hybridisation(e.g. microarrays, blots, hybridisation with probe in solution etc.).

A process for detecting wild-type Chlamydia (preferably, C. trachomatis)is provided, comprising the steps of: (a) contacting an antibody of theinvention with a biological sample under conditions suitable for theformation of an antibody-antigen complex(es); and (b) detecting saidcomplex(es). This process may advantageously be used to diagnoseChlamydia infection.

General

The practice of the present invention will employ, unless otherwiseindicated, conventional methods of chemistry, biochemistry, molecularbiology, immunology and pharmacology, within the skill of the art. Suchtechniques are explained fully in the literature. See, e.g., Gennaro(2000) Remington: The Science and Practice of Pharmacy. 20th edition,ISBN: 0683306472; Methods In Enzymology (S. Colowick and N. Kaplan,eds., Academic Press, Inc.); Handbook of Experimental Immunology, Vols.I-IV (D. M. Weir and C. C. Blackwell, eds, 1986, Blackwell ScientificPublications); Sambrook et ul. (2001) Molecular Cloning: A LaboratoryManual, 3rd edition (Cold Spring Harbor Laboratory Press); Handbook ofSurface and Colloidal Chemistry (Birdi, K. S. ed., CRC Press, 1997);Ausubel et al. (eds) (2002) Short protocols in molecular biology, 5thedition (Current Protocols); Molecular Biology Techniques: An IntensiveLaboratory Course, (Ream et al., eds., 1998, Academic Press); and PCR(Introduction to Biotechniques Series), 2nd ed. (Newton & Graham eds.,1997, Springer Verlag) etc.

“GI” numbering is used herein. A GI number, or “GenInfo Identifier”, isa series of digits assigned consecutively to each sequence recordprocessed by NCBI when sequences are added to its databases. The GInumber bears no resemblance to the accession number of the sequencerecord. When a sequence is updated (e.g. for correction, or to add moreannotation or information) then it receives a new GI number. Thus thesequence associated with a given GI number is never changed.

Where the invention concerns an “epitope”, this epitope may be a B-cellepitope and/or a T-cell epitope. Such epitopes can be identifiedempirically (e.g. using PEPSCAN (Geysen el al. (1984) PNAS USA81:3998-4002; Carter (1994) Methods Mol Biol 36:207-23) or similarmethods), or they can be predicted (e.g. using the Jameson-Wolfantigenic index (Jameson, B A et al. 1988, CABIOS 4(1):181-186),matrix-based approaches (Raddrizzani & Hammer (2000) Brief Bioinform1(2):179-89), MAPITOPE (Bublil et al. (2007) Proteins 68(l):294-304),TEPITOPE (De Lalla et al. (1999) J. Immunol. 163:1725-29; Kwok et al.(2001) Trends Immunol 22:583-88), neural networks (Brusic et al. (1998)Bioinformatics 14(2):121-30), OptiMer & EpiMer (Meister et al. (1995)Vaccine 13(6):581-91; Roberts et al. (1996) AIDS Res Hum Retroviruses12(7):593-610), ADEPT (Maksyutov & Zagrebelnaya (1993) Comput ApplBiosci 9(3):291-7), Tsites (Feller & de la Cruz (1991) Nature349(6311):720-1), hydrophilicity (Hopp (1993) Peptide Research6:183-190), antigenic index (Welling et al. (1985) FEBS Lett.188:215-218) or the methods disclosed in Davenport et al. (1995)Immunogenetics 42:392-297; Tsurui & Takahashi (2007) J Pharmacol Sci.105(4):299-316; Tong et al. (2007) Brief Bioinform. 8(2):96-108 ;Schirle et al. (2001) J Immunol Methods. 257(1-2):1-16; and Chen et al.(2007) Amino Acids 33(3):423-8, etc.). Epitopes are the parts of anantigen that are recognised by and bind to the antigen binding sites ofantibodies or T-cell receptors, and they may also be referred to as“antigenic determinants”.

Where an antigen “domain” is omitted, this may involve omission of asignal peptide, of a cytoplasmic domain, of a transmembrane domain, ofan extracellular domain, etc.

The term “comprising” encompasses “including” as well as “consisting”e.g. a composition “comprising” X may consist exclusively of X or mayinclude something additional e.g. X+Y.

The term “about” in relation to a numerical value x is optional andmeans, for example, x+10%.

References to a percentage sequence identity between two amino acidsequences means that, when aligned, that percentage of amino acids arethe same in comparing the two sequences. This alignment and the percenthomology or sequence identity can be determined using software programsknown in the art, for example those described in section 7.7.18 ofCurrent Protocols in Molecular Biology (F. M. Ausubel et al., eds.,1987) Supplement 30. A preferred alignment is determined by theSmith-Waterman homology search algorithm using an affine gap search witha gap open penalty of 12 and a gap extension penalty of 2, BLOSUM matrixof 62. The Smith-Waterman homology search algorithm is disclosed inSmith & Waterman (1981) Adv. Appl. Math. 2: 482-489.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a graph which shows the ability of 20 selected C. trachomatisantigens to induce IFNγ production by CD4+ T cells.

FIG. 2a shows the bacterial shedding (IFUs recovered from lungs) afterChlamydia challenge in mice to whom EB-CM CD4+ T cells had beenadoptively transferred. FIG. 2b shows the ability of various C.muridarum antigens to stimulate the protective EB-CD4+ T cell line toproduce IFNγ.

FIG. 3 is a histogram which shows the number of CD4+ T cells thatproduce IFNγ, upon specific stimulation with C. trachomatis recombinantantigens CT153 and CT733.

FIG. 4 shows the protective activity of TC0106 (C. muridarum homologueof CT733) and TC0431 (C. muridarum homologue of CT153) as singleantigens. The graph shows mean IFU/ml in BALB/C mice immunised with thetwo antigens and then challendged with C. muridarum. The three bars are,from left to right: adjuvant alone; TC0106 as immunogen; and TC0431 asimmunogen.

FIG. 5 shows the protective activity of the combination TC0106+TC0431.The graph shows mean IFU per lung (Log 10) recovered from infected lungsof mice immunised with the combination. The three bars are, from left toright: 10³ live Ebs; adjuvant alone; antigen combination.

FIG. 6 shows CD4 T cells producing IFNγ in PBMC of mice immunized withTC0106+TC0431, TC0106, TC0431 and LTK 63+CpG. From left to right, thebars represent stimulation with 1) LTK 63, TC0106+TC0431, TC0106, TC0431(all EB-immunized mice); 2) LTK 63, TC0106+TC0431, TC0106 (all TC0106-immunized mice); 3) LTK63, TC0106+TC0431. TC0431 (allTC0431-immunized mice); and 4) LTK63 and TC0106+TC0431 (bothTC0106+TC0431-immunized mice).

It shows that immunization with TC0106 (C. muridarum homologue of CT733)and TC0431 (C. muridarum homologue of CT153) elicits a significantfrequency of specific CD4+/IFNγ+ cells. The Y axis shows frequency on10⁶ CD4.

FIG. 7 is a summary of protection results for various combinations andsingle antigens in the mouse model of C. muridarum intransal challenge.It shows the mean IFU/lung of mice immunised imtramuscularly with singleantigens, or antigen combinations, adjuvanted with LTK63 and CpG, thenchallenged intranasally with 10³ C. muridarum IFU.

FIG. 8 is a summary of protection results for various combinations ofantigens in the mouse model of C. muridarum intransal challenge. Itshows mean IFU/lung (log 10) of C. muridarum recovered from infectedlungs of immunised mice.

FIG. 9 shows the results of the combination TC0551+TC0651+TC0727+TC0890in the mouse model of ovarian bursa challenge with C. muridarum. The Yaxis shows IFU/swab (lo g10). The three groups, from left to right, arefor different immunizing antigens: ovalbiumin; the combination; andnMOMP.

FIG. 10A shows the protection results achieved with various antigenscombinations in the mouse model of C. muridarum intranasal challenge.FIG. 10B shows the frequency of IFNg-producing CD4+ T cells induced byvaccination with the antigen combination TC0890+TC0551. From left toright, the bars represent stimutaion with 1) TC0551, TC0890,TC0551+TC0890 (for adjuvant-immunized mice) and 2) TC0551, TC0890,TC0551+TC0890 (for MIX TC0890+TC0551-immunized mice). FIG. 10C shows CD4T cells producing TFNg and IL2/TNF in PBMC of mice immunized withTC0106+TC0431 with Ltk63 +CpG. From left to right, the bars representstimulation with a) TC0106. TC0431, TC0106+TC0431, CT153+CT733 (alladjuvant-immunized mice); 2) TC0106, TC0431, TC0106+TC0431, CT153+CT733(all MIX TC0106+TC0431-immunized mice).

FIG. 11 shows an immunoblot analysis of CT601, CT279, CT153 and CT733 inCt-EBs and C. trachomatis-infected HeLa cells using their specific mouseimmune antisera.

FIG. 12 shows protective activity of antigens TC0313, TC0741, TC0106 andTC0210 given singly or in combination. In 12A to 12D the bars show meanIFU/lung (Log 10), with the left-hand bar being adjuvant alone(LTK61+CpG) and the right-hand bar being the TC antigen. FIG. 12E showsthe IFU reduction over time (Mean IFU/lung against days post-challenge)using the combination (squares) or adjuvant alone (diamonds).

FIGS. 13A and 13B are histograms showing the antigen specific CD4 Th1response in BALB/c mice after a primary C. trachomatis (CT) infection.Results are the mean of 4 independent experiments. Two results are shownfor each experiment: non-infected mice (left hand bar) and primaryinfected mice (right hand bar). From left to right in FIG. 13A, theresults relate to stimulation with CT812C, CT387, CT869, CT166 andCT175. From left to right in FIG. 13B, the results relate to stimulationwith MOMP, CT163, CT812, CT812C, CT166, CT869, CT163, CT812, CT214,CT387, CT721, CT127 and CT175. The frequency on 10⁵ CD4 T cells is shownon the Y axis.

FIG. 14 is a histogram showing C. muridarum IFUs recovered from infectedlungs of immunised mice (Day 12 post I.N. challenge with 10³ IFUs). Theimmunisation group is shown on the X axis: the left hand bar relates tomice immuised with LTK63+CpG; the right hand bar relates to miceimmunised with TC0197+TC0261+TC0666+LTK63+CpG. Mean IFU/lung (Log 10) isshown on the Y axis.

FIG. 15 is a histogram showing C. muridarum IFUs recovered from infectedlungs of immunised mice (Day 12 post I.N. challenge with 10³ IFUs). Theimmunisation group is shown on the X axis: from left to right, theresults relate to mice immunised with i) LTK63+CpG, ii)TC0261+LTK63+CpG, iii) TC0197+LTK63+CpG, and iv) TC0666+LTK63+CpG. MeanIFU/lung (Log 10) is shown on the Y axis.

MODES FOR CARRYING OUT THE INVENTION Example 1 Induction of Populationof CD4+ T Cells to Produce IFNγ

20 antigens have been found which induce a population of CD4+ T cells toproduce IFNγ (see FIG. 1). 17 of these are newly discovered (CT016,CT043, CT114, CT153, CT255, CT279, CT341, CT372, CT480, CT600, CT601,CT711, CT716, CT733, CT734. CT745, CT823), while three antigens(CT681-MOMP, CT396-Hsp60 and CT587-Enolase) have already been describedas targets of CD4+ T cells (Goodall J C et al. 2001; Hassell A B et al.1993). Significantly, some antigens were able to induce a frequency ofantigen-specific CD4+ responding T cells at least comparable to whatobserved with the positive control antigen MOMP.

The 17 new antigens are as follows:

Antigen Annotation Gene name CT016 Hypothetical protein CT043Hypothetical protein CT114 Hypothetical protein CT153 Hypotheticalprotein CT255 Hypothetical protein CT279 Na(+)-translocatingNADH-quinone nqr3 reductase subunit C CT341 Heat shock protein J (Hsp-J)dnaJ CT372 Hypothetical protein CT480 Oligopeptide Binding LipoproteinoppA_4 CT600 CT601 Invasin repeat family phosphatase papQ CT711Hypothetical protein CT716 Hypothetical protein CT733 Hypotheticalprotein CT734 Hypothetical protein CT745 protoporphyrinogen oxidase hemGCT823 DO serine protease htrA

Of these 17 new antigens, CT341 may be the least suitable for use inimmunization because it is a heat shock protein.

Example 2 Characterization of the Antigen-Specifity of ProtectiveChlamydia Specific CD4+ Th1 Cell Lines

The relevance of the newly discovered antigens for protective immunityto Chlamydia was further corroborated by showing that they wererecognized by T cells belonging to a Chlamydia-specific CD4+/IFNγ+ cellline, conferring protection when adoptively transferred to naïverecipient mice. To this aim we have derived a short-term CD4+ T cellline, produced against the extracellular EB form of C. muridarum thatshowed a high capacity to protect adoptively transferred naïve mice fromC. muridarum challenge. The protective CD4+ cell line, which hadundergone only a few cycles of expansion, maintained a polyclonal cellpopulation with broad specificity that should correlate more closely tothe in vivo protective response than long-term lines or clones. Thepolyclonal cell line was analysed for its antigen recognition profileversus the C. muridarum antigens, homologous to the C. trachomatisCD4-Th1 inducing proteins. The dissection of the antigen specificity ofthe protective CD4+ T cell polyclonal population demonstrated that theChlamydia CD4+/IFNγ+ inducing-antigens identified during an infectionare also targets of CD4+ T cells that play a part in the rapid clearanceof the bacterium in a protective response to the infection, in theabsence of antibodies.

Chlamydia T cell lines were derived from Balb/c infected mice and theirprotective activity was verified in naïve mice against C. muridarumchallenge. Subsequently, the antigen recognition profile of the C.muridarum. CD4+ T cell line was characterized to define the possiblecontribution of each C. muridarum antigen in inducing protective CD4+ Tcells. For the preparation of Chlamydia—specific CD4+ T cells, splenicCD4+ T lymphocytes were purified from donor Balb/c mice that hadpreviously been infected intranasally with 10³ viable Elementary Bodies(EBs) of C. muridarum. An EB-responding CD4+ T cell line was derived(referred as EB-CD4+ cell line) and expanded in vitro with a short termstimulation with heat inactivated EBs. The line showed the capacity torespond to C. muridarum EBs by producing IFNγ with a high frequency(data not shown). To determine the efficacy of the EB-CD4+ cell line inresolving an infection, 10⁷ CD4+ T cells were adoptively transferredinto 4 Balb/c recipient naïve mice. Mice were challenged intranasally 24hours after i.v. infusion of CD4+ T cells with 10³ IFUs of C. muridarum.The protective effect of adoptive immunization was evaluated byquantitating the number of IFUs recovered from lungs taken 10 days afterChlamydia challenge. As shown in FIG. 2a , naïve mice adoptivelytransferred with EB-CM CD4+ T cells shed 3 Log₁₀ fewer IFUs in the lungs10 days after intranasal challenge with 10³ IFUs of C. muridarum, ascompared to either non treated mice (p value: 0.008) or mice receivingan unrelated CD4+ T cell line. Similarly, splenic CD4+ T cells isolatedfrom mice that resolved an intravaginal primary infection with 10⁵ IFUsof C. trachomatis conferred significant IFU reduction in adoptivelytransferred mice (data not shown).

To characterize the antigen recognition profile of the C. muridarum CD4+T cells, most of the C. muridarum proteins, homolog of the proteinsidentified as CD4+ Th1 inducers during C. trachomatis infection (FIG.1), were obtained in recombinant form and tested for their ability tostimulate the protective EB-CD4+ T cell line to produce IFNγ. In thisanalysis we excluded both the proteins which after purification did notreach the purity/endoxin level required for the cytokine stimulationassay, or those which, due to their homology with human bacterialproteins were not suitable for developing a vaccine (e.g. heat shockproteins, enolase). The protective EB-CD4+ T cell line was stimulated invitro with a panel of 19 C. muridarum recombinant proteins, includingMOMP. Fourteen of them were homologs of C. trachomatis CD4+ Th1 inducingantigens identified in the primary screening in infected mice, and 5were negative controls. As shown in FIG. 2b , all the 14 CD4+-inducingantigens tested were found also to be targets of the protective EB-CMCD4+ T cell line, and able to induce IFNγ production in a percentage ofCD4+ T cells at least 3 times higher than the frequency of negativecontrol antigens. Therefore the pattern of T cell antigens recognized bythe protective Chlamydia EB-CM T cell line is comparable to therecognition profile of T cells identified in the C. trachomatis infectedmice.

Example 3 CT733 and CT153 Specific CD4+ Th1 Response in BALB/c Miceafter a Primary C. trachomatis Infection

Splenocytes of primary infected BALB/c mice and non infected controlswere collected 10 days after infection and stimulated with LPS-freerecombinant antigens CT733 and CT153 (20 mg/ml). After 4 hours ofstimulation, 5 mg/ml of Brefeldin A were added to the cells for thefollowing 12 hrs to block cytokine secretion. Afterwards, cells werefixed, permeabilized and stained. Intracellular IFNγ and IL-5 expressionwere analyzed versus CD4 surface expression of the gated viable cellsand assessed by flow cytometry.

The histogram in FIG. 3 shows the number of CD4+ T cells per 10⁵ CD4+ Tsplenocytes of primary infected (dark gery bars) and non-infected (lightgrey bars) mice that produce IFNγ upon specific stimulation with the C.trachomatis recombinant antigens CT153 and CT733. The data wereconfirmed in several further experiments using the same protcol.

The results indicate that CT733 and CT153 are able to induce significantfrequencies of specific CD4+/IFNγ+ cells in splenocytes from Balb/c micethat were infected intravaginally with C. trachomatis, suggesting apotential role as antigen candidates for these proteins.

Example 4 Protective Activity of Single Antigens TC0106 and TC0431Against C. muridarum Challenge

CT733 and CT153 were tested in a mouse model of chlamydial infection toevaluate their protective properties. This was done by adopting themouse model of lung infection with the species Chlamydia muridarum.

The C. muridarum proteins TC0106 and TC0431, homologous to CT733 andCTI53, respectively, were cloned and purified, and used for the mousemodel.

Groups of BALB/c mice were immunized with either TC0106 or TC0431recombinant antigens formulated with LTK63+CpG adjuvant (3 doses of 15ug protein, at 2 week interval, given intramuscularly). As negativecontrol, mice were immunized with the adjuvant only. Four weeks afterthe last immunization animals were infected intranasally with 10³ IFU ofinfectious C. muridarum. After 10 days, the protective activityconferred by the two antigens was measured by counting the infectiousIFU in the lung of challenge animals.

As shown in FIG. 4, each of the two antigens (middle and right handcolumns of the histogram) was able to reduce significantly the number ofIFU/lung in challenged mice as compared to adjuvant immunized mice (lefthand column of the histogram), indicating that both TC0106 and TC0431(and therefore CT733 and CT153) confer protective immunity to Chlamydiainfection

Example 5 Protective Activity of the Combination of TC0106+TC0431Against C. muridarum Challenge

Groups of BALB/c mice (10 to 15 mice) were immunized with thecombination of TC0106+TC0431 recombinant antigens formulated withLTK63+CpG adjuvant (3 doses of 10 ug of each protein at 2 week-interval,given intramuscularly). As negative control, mice were immunized withthe adjuvant only. Four weeks after the last immunization, animals wereinfected intranasally with 10³ 1FU of infectious C. muridarum. After 10days, the protective activity conferred by the two antigens was measuredby counting the infectious IFU in the lung of challenge animals. Aspositive control, a group of mice receiving a primary and a secondary C.muridarum infection was also included (left column in the histogram ofFIG. 5).

As shown in FIG. 5, the antigen combination (right hand column ofhistogram) was able to significantly reduce the number of IFU/lung inchallenged mice as compared to adjuvant immunized mice (middle column ofhistogram).

Thus, immunization with the CT733 and CT153, either alone or incombination, was able to significantly reduce the bacterial load in thelungs of challenged mice (see FIGS. 4 and 5).

Example 6 Elicitation of CD4+ Th1 Cells in BALB/c Mice afterImmunization with TC0431 and TC0106 Recombinant Antigens, Alone or inCombination

Groups of BALB/c mice (10 to 15 mice) were immunized with therecombinant antigens TC0431 and TC0106 as single antigens or incombination (i.m., 10-15 micrograms/dose, 3 doses at 2 week-intervals)using LTK63+CpG adjuvant. Ten days after the third immunization dose,splenocytes were collected and stimulated with LPS-free recombinantantigens (20 mg/ml). As negative control, splenocytes of adjuvantimmunized mice were included. After 4 hours of stimulation, 5 mg/ml ofBrefeldin A was added to the cells for the following 12 hrs to blockcytokine secretion. Afterwards, cells were fixed, permeabilized andstained. The intracellular IFNγ was analyzed versus CD4 surfaceexpression of the gated viable cells and assessed by flow cytometry. Thehistogram in FIG. 6 shows the number of CD4+ T cells per 10⁵ CD4+ Tsplenocytes that produce IFNγ upon specific stimulation with therecombinant antigens in mice immunized with TC0106, TC0431, thecombination of TC0106+TC0431 and adjuvant immunized mice.

The results indicate that immunization with these antigens elicits ahigh frequency of CD4+ Th1 cells.

Example 7 Evaluation of the Protective Effect of the ChlamydialAntigen(s) Against C. muridarum Challenge

The protective effect of combinations of two antigens selected from C.trachomatis CT279, CT601, CT372, CT443, CT733, CT153, CT456 and CT38Iwas tested in the C. muridarum mouse model using their C. muridarumhomologues TC0551 (CT279), TC0651 (CT372), TC0727 (CT443), TC0890(CT601), TC0106 (CT733), TC0431 (CT153), TC0660 (CT381) and TC0741(CT456). The protective effect of CT733 and CT153 individually was alsotested.

BALB/c mice were immunized three times intramuscularly with acombination of two antigens or single antigens with LTK63+CpG asadjuvant. Twenty-four days post last immunization mice were challengedintranasally with 10³ IFU C. muridarum. After 10 days, lungs werecollected, homogenized and the number of viable chlamydiae (IFU/lung)was measured. The data in FIG. 7 shows the mean IFU/lung counts inantigen-immunized mice and adjuvant-immunized control. From left toright, the lanes relate to (a) adjuvant only; (b) TC0551+TC0890(CT279+CT601); (c) TC0651+TC0727 (CT372+CT443); (d) TC0106+TC0431(CT733+CT153); (e) TC0660+TC0741 (CT456+CT381); (f) TC0106 (CT733); (g)TC0431 (CT153). For each antigen formulation, the numbers of infectedmice out of the total immunized are reported in the form “Inf X/Y”,wherein X is the number of infected mice and Y is the total number ofmice challenged. The statistical significance of immunizing antigen/s(P), was determined by Student t-test.

Four combinations of two antigens have been identified as capable ofconferring protection against C. muridarum intranasal challenge. Forthree of them (TC0431+TC0106; TC0727+TC0651; TC0551+TC0890; homologs ofCT733+CT153; CT443+CT372; CT279+CT601) protection has been confirmed ina high number of mice using LTK63+CpG adjuvant (FIG. 7). Immunizationexperiments with TC0431 and TC0106 (CT153 and CT733) as single antigensindicate that the two antigens are both immunogenic individually andthat either of the two antigens contributes to protection of theCT153+CT733 combination (FIG. 7). A fourth antigen combination has beenrecently identified (TC660+TC0741; homologs of CT456 and CT381) showingprotection in an immunization experiment (15 mice) (FIG. 7).

The experiments were repeated where the protocol differed from thatdescribed above in that the mice were challenged intranasally with 10³IFUs of C. muridarum three weeks after the last immunization. Sincedifferences in the duration of infections in the animals may occur, thepresence of infectious Chlamydiae in the lungs was determined in eachmouse at days 10 and 12 after challenge. Immunization experiments wererepeated at least three times so as to generate data from astatistically significant number of mice. FIG. 8 reports the mean numberof infectious chlamydiae recovered from lungs of mice immunized witheach antigen formulation, in which data obtained at days 10 and 12 wereaveraged. As shown in FIG. 8, two of the four combinations tested in themouse model, namely TC0551 (CT279 homolog, 82.6% identity)+TC0890(CT0601 homolog, 87.6% identity) and TC0106 (CT733 homolog, 84.8%identity) +TC0431 (CT153 homolog, 64.6% identity), showed astatistically significant protective effect in the immunized groups withan IFU reduction of more than 1 Log as compared to the adjuvant-injectedmice (P:<0.001). Moreover, 20-25% of the animals immunized with eitherof the two combinations resolved completely the infection by days 10-12,as compared to 9% of the adjuvant group.

Example 8 Evaluation of the Protective Activity of the CombinationTC0551+TC0890+TC0106+TC0431 Against Challenge with C. muridarum

On the basis of the result discussed in the preceeding Example, groupsof mice were immunized with a combination of four antigensTC0551+TC0890+TC0106+TC0431 using the same immunization regimen as inthe Example above. As shown in FIG. 8, the 4-antigen combinationappeared to have an additive protective effect over the 2-antigencombinations, showing 2.2 Logs reduction of bacterial shedding in thelung (P:0.0003). Moreover, 39% of animals totally resolved theinfection, indicating a higher efficacy of this antigen combination inaccelerating the bacterial clearance.

The remarkable reduction observed in the number of viable Chlamydiaerecovered from the lungs of immunized mice is the first demonstration ofa high level of protection induced by systemic immunization withrecombinant Chlamydia proteins. It has also to be pointed out that,since denatured forms of the recombinant antigens were used, furtheroptimization of antigen conformation could maximize their protectiveactivity.

Preliminary data aimed at defining whether any of the 4 recombinantantigens were protective when given as single antigens, indicated that alower level of IFU reduction was observed (less than 1 log) was obtainedwith any of them (data not shown). This is in agreement with the notionthat, in general, combinatorial vaccination approaches are moreeffective in conferring protective immunity against a given pathogenthan single vaccine approaches, since elicited immune responses targetdifferent aspects of the bacterial developmental cycle.

Example 9 Evaluation of the Protective Activity of the CombinationTC0551+TC0651+TC0727+TC0890 Against Intraovarian Bursa Challenge with C.muridarum

The protective effect of the combination TC0551+TC0651+TC0727+TC0890(homologs of C. trachomatis CT279+CT372+CT443+CT601) was tested in themouse model of ovarian bursa challenge with C. muridarum using theMontanide+CpG adjuvant. This model has previously been described toassess the protective activity of native MOMP (nMOMP), the chlamydialmajor outer membrane protein (Pal S et al, Infect Immun., 73:8153,2005). In this model, the protective activity of the antigens isassessed against progression of infection by counting the chlamydiashedding in vaginals swabs.

BALB/c mice were immunized three times intranasally with a combinationof the four antigens or with MOMP, with LTK63+CpG as adjuvant. Asnegative control, a group of mice immunized with ovalbumin was alsoincluded. Four weeks after the last immunization, mice received a C.muridarum challenge in the ovarian bursa and chlamydial shedding wasmeasured by counting the IFU in the vaginal swabs of infected animals.

The results shown in FIG. 9 represent the number of IFU/vaginal swab attwo weeks post challenge. As shown in FIG. 9, mice receiving thecombination of all four antigens show a reduced bacterial shedding ascompared to the negative control group (Ovalbumin). Thus, thecombination reduced the progression of infection. Interestingly, theprotection level obtained with the combination does not differsignificantly from that obtained with nMOMP, which is the mostprotective antigen that has been identified so far. Thus, thiscombination of four antigens is a particularly immunogenic combination.

Example 10 Antigen-Specific Cytokine Profiles of Protective CD4+ T Cells

Given the importance of the CD4-Th1 response in mediating protectionfrom Chlamydia infection, the type of immune response induced byvaccination with two antigen combinations that elicited protection inmice was analysed (TC0551+TC0890 and TC0106+TC0431). In particular, wemeasured the simultaneous production from antigen-specific CD4+ T cellsof IFNγ, TNF-α and 1L-2, considering this as an indication of optimaleffector functions of CD4+ T cells, possibly improving protection forvaccines aimed at targeting T-cell responses. The assessment of thecytokine profile induced in a single antigen specific CD4+ T cell byvaccination was performed by multiparametric flow cytometric analysis(Perfetto SP et al., Nat.Rev.Immunol. 4, 648-655, 2004) in immunizedmice. Peripheral blood was collected 12 days after the last immunizationwith antigen combinations TC0551+TC0890 and TC0106+TC0431. PBMC wereprepared and the frequency of CD3+, CD4+ antigen-specific IFNγ, IL-2 andTNF-producing cells was assessed by intracellular cytokine staining andflow cytometric determination. As shown in FIG. 10B, vaccination withthe antigen combination TC0551-TC0890 induced a high frequency ofTC0551-responding CD4+ T cells producing IFNγ (93 TC0551 specific CD4+ Tcells on 10⁵ CD4+ cells), while the response to TC0890 was very low,with a frequency of 16 IFNγ+ responding T cells on 10⁵ CD4+ cells. Theresponse to the antigen combination used for immunization showed anincreased response compared to single antigens, with 132 IFNγ producingT cells on 10⁵ CD4+ cells. Furthermore, there was a predominantfrequency of multifunctional CD4+ T cells, producing either IFNγ andTNF-α or IFNγ/TNF-α/IL-2 simultaneously. In the control group of mockimmunized mice there was no cytokine secretion in response to anyrecombinant antigen used for stimulation, indicating the specificity ofthe response observed in the vaccinated mice. As far as the CD4+response to the antigen combination TC0106-TC0431 is concerned (FIG.10C) both antigens, TC0106 and TC0431 induced a similar response with afrequency respectively of 120 and 98 IFNγ antigen-specific T cells on10⁵ CD4+, while the antigen combination showed a frequency of 145 IFNγ+responding T cells on 10⁵ CD4+ cells. The further analysis of cytokinesproduced simultaneously with IFNγ showed that about 50% of IFNγ+ cellsproduced also TNF-α and IL-2, while about 30% of them produced TNF-α.Overall these data underline that the Th1 cytokines produced byantigen-specific CD4+ T cells induced by vaccination showed a functionaldifference that could reflect differences in the capacity to clear theinfection.

Example: 11 Expression Analysis of CD4+ inducing Chlamydia Antigens

We then investigated the expression of CT279 (subunit C ofNa(+)-translocating NADH-quinone reductase), CT601 (Invasin repeatfamily phosphatase), CT733 (-Hypothetical protein) and CT153(MAC-Perforin Protein) by immunoblot analysis both in Ct-EBs and withinC. trachomatis infected HeLa cells, using their specific mouse immuneantisera (FIG. 11A). Total protein lysates of renografin-purified EBs(corresponding to approximately 10⁷ EBs per lane) showed that eachtested antiserum was able to react with a protein band of the expectedmolecular weight in both EB samples, showing in general a higherreactivity against CM EBs. For analysis of antigen expression inChlamydia-infected cells, total protein extracts were prepared from Hela229 cells at different time points after infection (24-48-72 h) andtested by immunoblot.

The amount of Chlamydial proteins loaded on the gel was normalized onthe basis of MOMP expression as described. As shown in FIG. 11B, thefour antigens appeared to be expressed at different phases of theChlamydia development.

Finally, we also investigated antigen cellular localization withininfected HeLa cells by confocal microscopy in infected Hela cells at 6,24, 48 and 72 h post infection. As shown in FIG. 11B, expression of allantigens was clearly detected within the inclusions at 24h postinfection and was still visible at 72 h. Interestingly, CT153 stainingappeared to accumulate at the inclusion membrane while the otherproteins were homogeneously distributed. Since CT153 encodes aMAC-Perforin protein, belonging to a protein family capable ofdisrupting the cell membrane, the ammassing of this protein at theinclusion membrane might anticipate its involvement in the Chlamydiaexit from infected cells.

The analysis of the immune response after vaccination with thecombinations has shown that all the recombinant antigens induced arobust humoral response, with the production of IgG2a antibody titershigher than IgGI, as expected for a Th1 driven immune response. Sincethe resolution of a Chlamydia infection requires a Th1 type of cellularimmune response, the regulation of CD4+ Th1 effector and memory cellsafter vaccination has also been investigated. Differences in the type ofcytokines produced by individual cells have important implications fortheir capacity to mediate effector functions, be sustained as memory Tcells or both. CD4+ T cells that secrete only IFNγ have limited capacityto develop into memory T cells as compared with IL-2-IFNγ doublepositive cells (Hayashi N. et al. 2002). Therefore vaccines elicitinghigh frequency of single-positive IFNγ producing cells may be limited intheir ability to provide long-lasting protection. Furthermore themajority of CD4+ T cells that produce IL-2, IFNγ and TNF are classifiedas effector memory cells, playing an essential role for mediatingprotection against intracellular pathogens (Darrah P A et al. 2007). Wedemonstrated that antigen-specific CD4+ T cells induced by immunizationwith the protective combinations were predominantly multifunctional,being differentiated to ensure a population of Th1 cells that includedeither effectors and memory cells. An appropriate balance of Th1 lineagecells that can be maintained and those with immediate protectivefunctions might be the successful formula for an effective vaccine.

Example 12 Combination of CT823+CT733+CT043+CT456

To evaluate the protective activity of antigens TC0106, TC0313, TC0210,TC0741 and their combination, groups of mice were immunized with the 4antigens either as single or in a 4 antigen-combination, using the sameimmunization regimen described in Example 7. The protective activity ofthe single antigens was assessed by measuring the IFU/Lung at day 12post infection. The protective activity of the 4-ag combination wasmeasured at days 10, 12, 14 post infection, to evaluate the kinetics ofthe infection clearance. As shown in FIG. 12, the single antigensconferred approximately 0.5-1 log IFU reduction in the lung of infectedanimals.

The four antigens combination showed a highest protective property,indicating a synergic activity of the four antigens in conferringprotection, eliciting approximately 4 logs reduction of bacterialshedding in the lung (P<0.0001) at day 12 and showing the tendency toresolve the infection at day 12. Moreover a high number of mice (42%)totally resolved the infection, indicating the efficacy of the antigencombination in accelerating the bacterial clearance.

Example 13 Evaluation of Antigenicity of CT812, CT387, CT869, CT166 andCT175

Antigen Specific CD4 Tg1 Response in BALB/c Mice After a Primary C.trachomatis (CT Infection

The antigen specific CD4 Th1 response in BALB/c mice after a primary C.trachomatis (CT) infection was evaluated. C. trachomatis antigensidentified by the proteomic characterization of the membrane fraction ofCT infected HeLa cells were tested for their capability to inducespecific CD4+ Th1 response in mice that received an experimental CTinfection. Splenocytes of primary infected BALB/c mice and non infectedcontrols were collected 10 days after infection and stimulated withLPS-free recombinant antigens (20 m/ml). After 4 hours of stimulation, 5μg/ml of Brefeldin A was added to the cells for the following 12 hrs, toblock cytokine secretion. Afterwards, cells were fixed, permeabilizedand stained. The intracellular IFN-γ expression was analyzed versus CD4surface expression of the gated viable cells, and assessed by flowcytometry. The histogram in FIG. 13A and FIG. 13B show the number ofCD4+ T cells that produce IFNγ, upon specific stimulation with CTrecombinant antigens per 10′ CD4+ T splenocytes of primary infected(right hand bars) and not-infected (left hand bars) mice. Data arerepresentative of 4 different experiments. As shown in FIG. 13A, CT812C,CT387, CT869 and CT166 induced a significant frequency of CD4⁺-IFNγ+cells in splenocytes of infected animals (Pval <0.05). As shown in FIG.13B, CT812C (a C-terminal fragment of CT812) surprisingly induced ahigher frequency of CD4⁺-IFNγ+ cells in splenocytes of infected animalsthan did the full length CT812 sequence.

Protective Activity of the Combination of TC0197+TC0261+TC0666 againstC. muridarum Challenge

The protective effect of the combination of the three C. trachomatisantigens CT387+CT812+CT869 was tested in the C. muridarum mouse modelusing their C. muridarum orthologues TC0666, TC0197 and TC0261,respectively. TC0197, TC0261 and TC0666 were cloned and purified forprotection studies in the mouse model of intranasal infection with C.muridarum. Groups of BALB/c mice (16 mice per group) were immunized withthe combination of the three recombinant antigens TC0197+TC0261+TC0666formulated with LTK63+CpG adjuvant (3 doses of 10 μg of each protein, at2 week-interval, given intramuscularly). As a negative control, micewere immunized with the adjuvant only. Four weeks after the lastimmunization, animals were infected intranasally with 10³ IFU ofinfectious C. muridarum. After 12 days, the protective activityconferred by the two antigens was measured by counting the infectiousIFU in the lung of challenge animals. As shown in FIG. 14, the antigencombination TC0197+TC0261+TC0666 was able to reduce significantly thenumber of IFU/lung in challenged mice as compared to adjuvant immunizedmice (1.4 log IFU reduction with Pval <0.05). The finding that thecombination of TC0197+TC0261+TC0666 is able to protect mice against C.muridarum challenge (FIG. 14) provides evidence that the combinationsCT812+CT869+CT387 and CT812C+CT869+CT387 from C. trachomatis areprotective against infection by C. trachomatis.

Protective Activity of TC0197, TC0261 and TC0666 as single antigensagainst C. muridarum Challenge

The protective activity of TC0197, TC0261 and TC0666 as single antigensagainst C. muridarum challenge was assessed. 3 Groups of BALB/c mice (16mice per group) were immunized with the three recombinant antigensindividually formulated with LTK63+CpG adjuvant (3 doses of 20 ug ofeach protein, at 2 week-interval, given intramuscularly). As a negativecontrol, mice were immunized with the adjuvant only. Four weeks afterthe last immunization, animals were infected intranasally (I.N.) with10³ IFU of infectious C. muridarum. After 12 days, the protectiveactivity conferred by the three single antigens was measured by countingthe infectious IFU in the lung of challenge animals. As shown in FIG.15, none of the 3 antigens individually were able to reducesignificantly the number of IFU/lung in challenged mice as compared toadjuvant immunized mice.

Thus, the combination of TC0197+TC0261+TC0666 is able to protect miceagainst C. muridarum challenge (FIG. 14). In particular, FIG. 14 showsprotection in terms of reduction in the mean number of IFUs recoveredfrom lungs of immunized mice versus adjuvant immunized controls[p=0.0024]. In contrast, the three antigens are not protective whenadministered individually (FIG. 15).

Example 14 Materials and Methods

The experimental protocols used in Examples 1, 2, 7 (repeatedexperiments), 8, 10 and 11 are described in further detail in thisExample.

Bacterial Strains, Cultures and Reagents

Chlamydia muridarum Nigg and Chlamydia trachomatis serovar D strainD/UW-3/CX were grown on confluent monolayers of LLCMK2 (ATCC CCL7) orHeLa 229 cells (ATCC CCL 2.1) in Earle minimal essential medium (EMEM)as described (Caldwell et al. (1981) Infect Immun 31: 1161-1176).Purification of C. trachomatis and C. muridarum EBs was carried out byRenografin density gradient centrifugation as described (Montigiani etal. (2002) Infect Immun 70: 368-379.). Bacteria were aliquoted andstored at −70° C. in sucrose-phosphate-glutamine buffer (SPG) until use.When indicated, EBs were heat inactivated at 56° C. for 3 hours.

E. coli DH5α or BL21 (DE3) was grown aerobically in Luria Broth (LB)medium (Difco) at 37° C. When appropriate, ampicillin (100 μg/ml) andisopropyl-beta-D-galactopyranoside (IPTG, 0.5 mM) were added to themedium.

Unless specified, all chemicals were purchased from Sigma. Restrictionenzymes and DNA modification enzymes were from New England Biolabs.Unless differently stated, all reagents and antibody for intracellularcytokine staining were from BD Biosciences Pharmingen. Confocalmicroscopy reagents were from Molecular Probes.

Gene Cloning, Protein Expression and Preparation of Antisera

To produce C. trachomatis recombinant proteins and their C. muridarumhomologs, genes were PCR-amplified from C. trachomatis and C. muridarumchromosomal DNA using specific primers annealing at the 5′ and 3′ endsof either gene. The genes were cloned into plasmid pET21b⁺ (lnvitrogen)or pGEXKG (Amersham) in order to express them both as a C-terminalHis-tag fusion and as a double fusion protein with an N-terminalGlutathione transferase-encoding sequence and a C-terminal His-tag.

Cloning and purification of His- and GST fusions were performed asalready described (Montigiani et al., 2002). CT0681 and TC0052, encodingfor C. trachomatis and C. muridarum MOMP respectively (Ct MOMP and CmMOMP, respectively) were expressed as His fusions and purified from theinsoluble protein fraction. With the exception of TC0313 and TC0210, allthe C. muridarum proteins used in this work were purified only from theinsoluble protein fraction in a denatured form.

For T cell in vitro stimulation assays, LPS-free proteins were preparedby washing of column-immobilized proteins with buffer Tris-HCl 10 mM, pH8, containing 1% Triton X114 (35 ml) at 4° C. The amount of residualendotoxin was determined using a Limulus Amebocyte Lysate Analysis Kit(QCL-100, BioWhittaker, Walkerville, Md.).

Mouse antisera were generated and treated as described (Montigiani etal., 2002). Where specified, sera from mice immunized with 20 μg of E.coli contaminant proteins (IMAC-purified proteins from E. coli bacteriacontaining pET21b+ empty vector) were used as negative control. Westernblot, ELISA and Flow cytometry of C. trachomatis EBs were performed asdescribed (Finco et al. (2005) Vaccine 23: 1178-1188.).

Screening of Antigen Specific CD4-Th1 Response in Splenocytes fromInfected Mice

Groups of 6 week-old female BALB/c mice purchased from Charles RiverLaboratories (3 mice/group) received a subcutaneus hormonal treatmentwith 2.5 mg of Depo-provera (Medroxyprogesterone acetate) and after fivedays mice were inoculated intravaginally with 15 μl of SPG buffercontaining 10⁶ of C. trachomatis IFU. The level of infection wasanalyzed 7 days post-challenge, by collecting vaginal swabs and countingchlamydial inclusions 48 h later stained with FITC-conjugated antiChlamydia antibody (Merifluor) using a UV microscope.

The swabs were collected in 400 μl of SPG and were inoculated on LLCMK2cell monolayers seeded on 96 w flat bottom plates. After 48 hoursincubation the number of infectious chlamydiae was determined bycounting chlamydial inclusions.

Ten days post challenge mice were sacrificed and their spleens weretaken. Splenocytes were prepared by homogenization through a nylonfilter (BD) and the erythrocytes were removed by hypotonic lysis in Acklysis buffer (NH₄Cl 0.155 M, KHCO₃ 10 mM, Na₂EDTA 0.1 mM) for 3 minutesat RT, then the cells were plated in 96 wells plates at 2×10⁶ cells perwell and stimulated with 20 μg/ml of endotoxin-free specific antigen orwith 4 μg/ml of purified EBS in presence of 1 μg/ml anti-CD28 antibody(BD Biosciences Pharmingen) for 4 h at 37° C. Brefeldin A (BFA;Sigma-Aldrich) was then added at a final concentration of 2.5 μg/ml andcells were incubated for an additional 16 h before intracellularcytokine staining. Cells were stained for viability with LIVE/DEAD®(Molecular Probes) dye according to the manufacturer's instructions.Cells were then fixed and permeabilized using the Cytofix/Cytoperm kit(BD Biosciences Pharmingen) and stained with fluorochrome-labelledmonoclonal antibodies for the detection of cells expressing CD3, CD4 onthe surface and intracellular IFNγ and IL-4. Finally, cells wereresuspended in PBS 1% BSA. All antibodies for intracellular cytokinestaining were purchased from BD Pharmingen. Acquisition of the sampleswas performed using a BD Canto flow cytometer and data were analyzedusing FlowJo software (Tree Star Inc., Ashland, USA). The intracellularexpression of IFNγ and IL-4 was analysed in CD4 expressing singletcells, previously gated for, morphology, CD3 expression and viability.Cells were then harvested and stained for CD4 surface expression andIFNγ, or IL-4 intracellular production, to investigate whether theobserved responses were of the Th1 (IFNγ) or Th2 (IL-4) type. Asnegative control, spleens from not infected mice were harvested andanalyzed in parallel.

Preparation of CD4+ Th1 Cell Lines and of Antigen Presenting Cells(APCs)

Splenocytes were prepared by homogenization from spleens from donorBalb/c mice that had previously been infected intranasally with 10³viable Elementary Bodies (EBs) of Chlamydia muridarum (C. muridarum) asdecribed above. Following centrifugation at 1200 rpm and suspension inMacs Buffer (PBS PH 7.2 0.5% BSA and 2 mM EDTA), the cells wereincubated with CD4 (L3T4) microbeads (Milteny Biotec) for 15 minutes andthen loaded on a LS columns. The CD4 cells bound to the magnet wererecovered, washed and suspended in RPMI 1640 supplemented with 2.5%fetal bovine serum (Hyclone), antibiotics, L-Glutammine 2 mM, SodiumPiruvate 1 mM, MEM Not essential amino Acids, MEM Vitamins (Gibco) andBeta-mercaptoethanol 0.5 μM. Then the cells were plated in 6 multiwellplates, 10⁷ cells/wells. After the first stimulation, the purified CD4were washed twice and then plated with APCs as described below.

Also a CD4+ cell line with C. trachomatis was obtained by spleens fromdonor Balb/c mice that had previously been infected intravaginally with10⁶ viable Elementary Bodies (EBs) of Chlamydia trachomatis and it wasperformed as described above for Chlamydia muridarum.

The CD4 cells were plated (6×10⁶/well) with APCs (2×10⁷/well) preparedby naive mice spleens. Splenocytes were prepared as described above,then were washed twice with the medium, gamma irradiated for 7 minuteswashed again and suspended in medium.

Cultures were then incubated at 37° C. in a humidified atmospherecontaining 5% CO₂. After 24 h, Aldesleukin Proleukin (IL2) was added ata concentration of 20U/ml.

C. muridarum and C. trachomatis-Mouse Model of Adoptive Transfer

Groups of 6 week-old female BALB/c mice purchased from Charles RiverLaboratories (4 mice/group), were adoptively transferred by intravenousadministration of 10⁷ CD4+ T cells in 100 ul of RPMI-1640 medium(Sigma). Mice were challenged intranasally 24 hours after with 10³ IFUsof C. muridarum or 10⁵ IFUs of C. trachomatis. The effect of adoptiveimmunization was evaluated by quantitating the number of IFUs recoveredfrom lungs taken 10 days after C. muridarum challenge or 6 days after C.trachomatis challenge, as described above.

Characterization of the C. muridarum CD4+ T Cell Line

The same day of the adoptive transfer, an aliquot of purified CD4+ Tcells were taken to assess the capability of C. muridarum antigensidentified in the previous CD4+ Th1+ screening to stimulate them invitro. 250000 cells/w were plated in 96 multiwell plates with 10⁶ mousesplenocytes CD4 depleted as APC and stimulated with 20 μg/ml of C.muridarum proteins, homologous to the C. trachomatis proteins identifiedas CD4+ Th1 inducers, in presence of 1 μg/ml anti-CD28 antibody (BDBiosciences Pharmingen) for 3 h at 37° C. Then BFA was added andintracellular staining was carried out as described for the splenocytes.

Mouse Protection Model

Groups of 6 week-old female BALB/c mice (10-15 mice/group), wereimmunized intramuscularly (i.m.) with 3 doses of the antigencombinations TC0551-TC890 (15 μg/close) and TC0106-TC0431 (containing 10μg of each protein/dose) at days 1, 15, and 28 formulated with 5 μg ofLTK63 (Ryan et al., 2000) +10 μg of CpG (ODN 1826) adjuvant dissolved in50 μl PBS. As negative control, groups of mice that received theadjuvant alone were included and treated in parallel.

Three weeks after the last immunization mice were inoculatedintranasally (i.n.) with 40 μl of SPG buffer containing 10³ IFU of C.muridarum. The Chlamydia challenge dose given to each mouse wasconfirmed by culturing in triplicate serial dilutions of the inoculatingdose on LLCMK2 cell monolayers seeded on 96 wells flat bottom plates.After 24 hours incubation the number of infectious chlamydiae wasdetermined by counting chlamydial inclusions. In the time period between10- and 12 days post challenge mice were sacrificed, lungs were isolatedand their homogenates were used to assess chlamydia growth.

Analysis of antigen specific CD4-Th1 response in PBMC of mice PBMC frommouse were isolated from up to 2 ml of heparinized blood, diluted 1/5 inHBSS (Hanks' Balanced Salt Solution) and separated by density gradientcentrifugation over Lympholite-M (Cedarlane). 10⁶ PBMC were plated induplicate in 96 multiwell plates with 10⁶ mouse splenocytes CD4 depletedas APC and stimulated and stained as described above for mousesplenocytes for 16 h. In this staining was analyzed the expression ofIFNγ, TNFα and IL-2.

Confocal Microscopy

To examine cellular localization of C. trachomatis proteins afterinfection, HeLa cells (20000) were plated on onto glass coverslides (Ø13mm) and after 24 hours were infected with CT EBs in 1:1 ratio asdescribed above. At 6, 24, 48 and 72 hours post infection the cells werefixed in 2% paraformaldehyde in PBS buffer for 20 minutes at roomtemperature. After 2 washes with PBS the cells were permeabilized with asolution of 1%/saponin-0.1% Triton in PBS for 20 minutes.

After washing twice and blocking with PBS containing 1% BSA (PBS-BSA),the cell samples were subjected to antibody and chemical staining. Thesamples were incubated for 1 h at RT (standard dilution 1:5000 inPBS-BSA) with polyclonal antisera obtained from mice immunized withTC601, TC279, TC733 and TC153, previously pre-adsorbed overnight at 4°C. onto nitrocellulose strips containing E. coli BL21 cell totalproteins. Goat anti-mouse Alexa Fluor (Molecular Probes) conjugatedantibodies (excitation at 488) were used to visualize the localizationof each antigen. Propidium Iodide and Phalloidin conjugated with AlexaFluor dye A620 (Molecular Probes) were used to visualize respectivelyDNA and actin.

After extensive washes in PBS, cells were mounted with Anti-Fade reagent(Molecular Probes) and observed under a laser scanning confocalmicroscope (Bio-Rad) with 100× oil immersion objective lens.

It will be understood that the invention has been described by way ofexample only and modifications may be made whilst remaining within thescope and spirit of the invention.

TABLE 2 C. pneumoniae accession number & annotation C. trachomatisaccession number & annotation CT No. Hypothetical protein (AAC67968)CT372 omcB (AAC68042) CT443 Hypothetical protein (AAC67634) CT043Hypothetical protein (AAC67744) CT153 Nqr3 (AAC67872) CT279 papQ(AAC68203) CT601 Hypothetical protein (AAC68306) CT711 Hypotheticalprotein (AAC67705) CT114 oppA_4 (AAC68080) CT480 Hypothetical protein(AAC68056) CT456 ArtJ (AAC67977) CT381 lcrE (AAC67680) CT089Hypothetical protein (AAC68329) CT734 Hypothetical protein (AAC67606)CT016 gi|4376729|gb|AAD18590.1|Polymorphic Outer Membranegi|3329346|gb|AAC68469.1|Putative Outer Membrane Protein G Protein GFamily gi|4376729|gb|AAD18590.1|Polymorphic Outer Membranegi|3329346|gb|AAC68469.1|Putative Outer Membrane Protein G Protein GFamily gi|4376731|gb|AAD18591.1|Polymorphic Outer Membranegi|3329346|gb|AAC68469.1|Putative Outer Membrane Protein G Protein G/IFamily gi|4376731|gb|AAD18591.1|Polymorphic Outer Membranegi|3329350|gb|AAC68472.1|Putative Outer Membrane Protein I Protein G/IFamily gi|4376731|gb|AAD18591.1|Polymorphic Outer Membranegi|3329346|gb|AAC68469.1|Putative Outer Membrane Protein G Protein G/IFamily gi|4376733|gb|AAD18593.1|Polymorphic Outer Membranegi|3328840|gb|AAC68009.1|Putative outer membrane protein A Protein GFamily gi|4376731|gb|AAD18591.1|Polymorphic Outer Membranegi|3329346|gb|AAC68469.1|Putative Outer Membrane Protein G Protein G/IFamily gi|4376754|gb|AAD18611.1|Polymorphic Outer Membranegi|3329344|gb|AAC68467.1|Putative Outer Membrane Protein E Protein(Frame-shift with C gi|4376260|gb|AAD18163.1|Polymorphic Outer Membranegi|3329346|gb|AAC68469.1|Putative Outer Membrane Protein G Protein GFamily gi|4376262|gb|AAD18165.1|hypothetical proteingi|3328765|gb|AAC67940.1|hypothetical proteingi|4376269|gb|AAD18171.1|hypothetical proteingi|3328825|gb|AAC67995.1|hypothetical proteingi|4376270|gb|AAD18172.1|Polymorphic Outer Membranegi|3329350|gb|AAC68472.1|Putative Outer Membrane Protein I Protein GFamily gi|4376272|gb|AAD18173.1|Predicted OMP {leader peptide:gi|3328772|gb|AAC67946.1|hypothetical protein CT351 outer membrane}gi|4376273|gb|AAD18174.1|Predicted OMP {leader peptide}gi|3328771|gb|AAC67945.1|hypothetical protein CT350gi|4376296|gb|AAD18195.1|hypothetical proteingi|3328520|gb|AAC67712.1|Ribulose-P Epimerasegi|4376362|gb|AAD18254.1|YbbP family hypothetical proteingi|3328401|gb|AAC67602.1|hypothetical proteingi|4376372|gb|AAD18263.1|Signal Peptidase Igi|3328410|gb|AAC67610.1|Signal Peptidase Igi|4376397|gb|AAD18286.1|CHLPS hypothetical proteingi|3328506|gb|AAC67700.1|CHLPS hypothetical proteingi|4376402|gb|AAD18290.1|ACR family gi|3328505|gb|AAC67699.1|ACR familygi|4376419|gb|AAD18305.1|CT149 hypothetical proteingi|3328551|gb|AAC67740.1|possible hydrolasegi|4376446|gb|AAD18330.1|hypothetical proteingi|3329261|gb|AAC68390.1|hypothetical proteingi|4376466|gb|AAD18348.1|Oligopeptide Binding Proteingi|3328604|gb|AAC67790.1|Oligopeptide Binding Protein CT198gi|4376467|gb|AAD18349.1|Oligopeptide Binding Proteingi|3328604|gb|AAC67790.1|Oligopeptide Binding Proteingi|4376468|gb|AAD18350.1|Oligopeptide Binding Proteingi|3328539|gb|AAC67730.1|Oligopeptide Binding Proteingi|4376469|gb|AAD18351.1|Oligopeptide Binding Proteingi|3328579|gb|AAC67766.1|Oligopeptide binding protein permeasegi|4376520|gb|AAD18398.1|Polysaccharide Hydrolase-Invasingi|3328526|gb|AAC67718.1|predicted polysaccharide Repeat Familyhydrolase-invasin repeat family gi|4376567|gb|AAD18441.1|InclusionMembrane Protein C gi|3328642|gb|AAC67825.1|Inclusion Membrane Protein Cgi|4376576|gb|AAD18449.1|Omp85 Analog gi|3328651|gb|AAC67834.1|Omp85Analog CT241 gi|4376577|gb|AAD18450.1|(OmpH-Like Outer Membranegi|3328652|gb|AAC67835.1|(OmpH-Like Outer Membrane CT242 Protein)Protein) gi|4376601|gb|AAD18472.1|Low Calcium Response Dgi|3328486|gb|AAC67681.1|Low Calcium Response Dgi|4376602|gb|AAD18473.1|Low Calcium Response Egi|3328485|gb|AAC67680.1|Low Calcium Response E CT089gi|4376607|gb|AAD18478.1|Phopholipase D Superfamilygi|3328479|gb|AAC67675.1|Phopholipase D Superfamily {leader (33)peptide} gi|4376615|gb|AAD18485.1|YojL hypothetical proteingi|3328472|gb|AAC67668.1|hypothetical protein CT077gi|4376624|gb|AAD18493.1|Solute Protein Binding Familygi|3328461|gb|AAC67658.1|Solute Protein Binding Familygi|4376639|gb|AAD18507.1|Flagellar Secretion Proteingi|3328453|gb|AAC67651.1|Flagellar Secretion Proteingi|4376664|gb|AAD18529.1|Leucyl Aminopeptidase Agi|3328437|gb|AAC67636.1|Leucyl Aminopeptidase A CT045gi|4376672|gb|AAD18537.1|CBS Domain protein (Hemolysingi|3328667|gb|AAC67849.1|Hypothetical protein containing Homolog) CBSdomains gi|4376679|gb|AAD18543.1|CT253 hypothetical proteingi|3328664|gb|AAC67846.1|hypothetical proteingi|4376696|gb|AAD18559.1|CT266 hypothetical proteingi|3328678|gb|AAC67859.1|hypothetical protein CT266gi|4376717|gb|AAD18579.1|Phospholipase D superfamilygi|3328698|gb|AAC67877.1|Phospholipase D superfamilygi|4376727|gb|AAD18588.1|Polymorphic Outer Membranegi|3329346|gb|AAC68469.1|Putative Outer Membrane Protein G Protein G/IFamily gi|4376728|gb|AAD18589.1|Polymorphic Outer Membranegi|3329346|gb|AAC68469.1|Putative Outer Membrane Protein G Protein GFamily gi|4376729|gb|AAD18590.1|Polymorphic Outer Membranegi|3329350|gb|AAC68472.1|Putative Outer Membrane Protein I Protein GFamily gi|4376731|gb|AAD18591.1|Polymorphic Outer Membranegi|3329350|gb|AAC68472.1|Putative Outer Membrane Protein I Protein G/IFamily gi|4376733|gb|AAD18593.1|Polymorphic Outer Membranegi|3328840|gb|AAC68009.1|Putative outer membrane protein A Protein GFamily gi|4376735|gb|AAD18594.1|Polymorphic Outer Membranegi|3328840|gb|AAC68009.1|Putative outer membrane protein A Protein(truncated) A/I Fam gi|4376736|gb|AAD18595.1|Polymorphic Outer Membranegi|3329346|gb|AAC68469.1|Putative Outer Membrane Protein G Protein GFamily gi|4376737|gb|AAD18596.1|Polymorphic Outer Membranegi|3329347|gb|AAC68470.1|Putative Outer Membrane Protein H Protein HFamily gi|4376751|gb|AAD18608.1|Polymorphic Outer Membranegi|3329344|gb|AAC68467.1|Putative Outer Membrane Protein E Protein EFamily gi|4376752|gb|AAD18609.1|Polymorphic Outer Membranegi|3329344|gb|AAC68467.1|Putative Outer Membrane Protein E Protein EFamily gi|4376753|gb|AAD18610.1|Polymorphic Outer Membranegi|3329344|gb|AAC68467.1|Putative Outer Membrane Protein E Protein E/FFamily gi|4376757|gb|AAD18613.1|hypothetical proteingi|3328701|gb|AAC67880.1|PP-loop superfamily ATPasegi|4376767|gb|AAD18622.1|Arginine Periplasmic Bindinggi|3328806|gb|AAC67977.1|Arginine Binding Protein CT381 Proteingi|4376790|gb|AAD18643.1|Heat Shock Protein-70gi|3328822|gb|AAC67993.1|HSP-70 CT396 gi|4376802|gb|AAD18654.1|CT427hypothetical protein gi|3328857|gb|AAC68024.1|hypothetical proteingi|4376814|gb|AAD18665.1|CT398 hypothetical proteingi|3328825|gb|AAC67995.1|hypothetical protein CT398gi|4376829|gb|AAD18679.1|polymorphic membrane protein Agi|3328840|gb|AAC68009.1|Putative outer membrane protein A Familygi|4376830|gb|AAD18680.1|polymorphic membrane protein Bgi|3328841|gb|AAC68010.1|Putative outer membrane protein B Familygi|4376832|gb|AAD18681.1|Solute binding proteingi|3328844|gb|AAC68012.1|Solute-binding protein CT415gi|4376834|gb|AAD18683.1|(Metal Transport Protein)gi|3328846|gb|AAC68014.1|(Metal Transport Protein)gi|4376847|gb|AAD18695.1|Tail-Specific Proteasegi|3328872|gb|AAC68040.1|Tail-Specific Proteasegi|4376848|gb|AAD18696.1|15 kDa Cysteine-Rich Proteingi|3328873|gb|AAC68041.1|15 kDa Cysteine-Rich Proteingi|4376849|gb|AAD18697.1|60 kDa Cysteine-Rich OMPgi|3328874|gb|AAC68042.1|60 kDa Cysteine-Rich OMP CT443gi|4376850|gb|AAD18698.1|9 kDa-Cysteine-Rich Lipoproteingi|3328876|gb|AAC68043.1|9 kDa-Cysteine-Rich Lipoprotein CT444gi|4376878|gb|AAD18723.1|2-Component Sensorgi|3328901|gb|AAC68067.1|2-component regulatory system- CT467 sensorhistidine kinase gi|4376879|gb|AAD18724.1|similarity to CHLPS IncAgi|3328451|gb|AAC67649.1|hypothetical proteingi|4376884|gb|AAD18729.1|CT471 hypothetical proteingi|3328905|gb|AAC68071.1|hypothetical proteingi|4376886|gb|AAD18731.1|YidD familygi|3328908|gb|AAC68073.1|hypothetical proteingi|4376890|gb|AAD18734.1|CT476 hypothetical proteingi|3328911|gb|AAC68076.1|hypothetical proteingi|4376892|gb|AAD18736.1|Oligopeptide Permeasegi|3328913|gb|AAC68078.1|Oligopeptide Permeasegi|4376894|gb|AAD18738.1|Oligopeptide Binding Lipoproteingi|3328915|gb|AAC68080.1|oligopeptide Binding Lipoproteingi|4376900|gb|AAD18743.1|Glutamine Binding Proteingi|3328922|gb|AAC68086.1|Glutamine Binding Proteingi|4376909|gb|AAD18752.1|Protease gi|6578107|gb|AAC68094.2|Proteasegi|4376952|gb|AAD18792.1|Apolipoprotein N-Acetyltransferasegi|3328972|gb|AAC68136.1|Apolipoprotein N-Acetyltransferasegi|4376960|gb|AAD18800.1|FKBP-type peptidyl-prolyl cis-transgi|3328979|gb|AAC68143.1|FKBP-type peptidyl-prolyl cis-trans CT541isomerise isomerise gi|4376968|gb|AAD18807.1|CT547 hypothetical proteingi|3328986|gb|AAC68149.1|hypothetical protein CT547gi|4376969|gb|AAD18808.1|CT548 hypothetical proteingi|3328987|gb|AAC68150.1|hypothetical proteingi|4376998|gb|AAD18834.1|Major Outer Membrane Proteingi|3329133|gb|AAC68276.1|Major Outer Membrane Protein CT681gi|4377005|gb|AAD18841.1|YopC/Gen Secretion Protein Dgi|3329125|gb|AAC68269.1|probable Yop proteins translocation proteingi|4377015|gb|AAD18851.1|FHA domain; (homology togi|3329115|gb|AAC68259.1|(FHA domain; homology to adenylate cyclase)adenylate cyclase) gi|4377033|gb|AAD18867.1|CHLPN 76 kDa Homolog_1gi|3329069|gb|AAC68226.1|CHLPN 76 kDa Homolog CT622 (CT622)gi|4377034|gb|AAD18868.1|CHLPN 76 kDa Homolog_2gi|6578109|gb|AAC68227.2|CHLPN 76 kDa Homolog CT623 (CT623)gi|4377035|gb|AAD18869.1|Integral Membrane Proteingi|3329071|gb|AAC68228.1|Integral Membrane Proteingi|4377072|gb|AAD18902.1|CT648 hypothetical proteingi|3329097|gb|AAC68825.1|hypothetical proteingi|4377073|gb|AAD18903.1|CT647 hypothetical proteingi|3329096|gb|AAC68824.1|hypothetical protein CT647gi|4377085|gb|AAD18914.1|CT605 hypothetical proteingi|3329050|gb|AAC68208.1|hypothetical proteingi|4377090|gb|AAD18919.1|Peptidoglycan-Associatedgi|3329044|gb|AAC68202.1|Peptidoglycan-Associated CT600 LipoproteinLipoprotein gi|4377091|gb|AAD18920.1|macromolecule transportergi|3329043|gb|AAC68201.1|component of a macromolecule transport systemgi|4377092|gb|AAD18921.1|CT598 hypothetical proteingi|3329042|gb|AAC68200.1|hypothetical proteingi|4377093|gb|AAD18922.1|Biopolymer Transport Proteingi|3329041|gb|AAC68199.1|Biopolymer Transport Protein CT597gi|4377094|gb|AAD18923.1|Macromolecule transportergi|3329040|gb|AAC68198.1|polysaccharide transportergi|4377101|gb|AAD18929.1|CT590 hypothetical proteingi|3329033|gb|AAC68192.1|hypothetical proteingi|4377102|gb|AAD18930.1|CT589 hypothetical proteingi|3329032|gb|AAC68191.1|hypothetical protein CT589gi|4377106|gb|AAD18933.1|hypothetical proteingi|3328796|gb|AAC67968.1|hypothetical proteingi|4377111|gb|AAD18938.1|Enolase gi|3329030|gb|AAC68189.1|Enolase CT587gi|4377127|gb|AAD18953.1|General Secretion Protein Dgi|3329013|gb|AAC68174.1|Gen. Secretion Protein Dgi|4377130|gb|AAD18956.1|predicted OMP {leader peptide}gi|3329010|gb|AAC68171.1|predicted OMP CT569gi|4377132|gb|AAD18958.1|CT567 hypothetical proteingi|3329008|gb|AAC68169.1|hypothetical protein CT567gi|4377133|gb|AAD18959.1|CT566 hypothetical proteingi|3329007|gb|AAC68168.1|hypothetical proteingi|4377140|gb|AAD18965.1|Yop Translocation Jgi|3329000|gb|AAC68161.1|Yop proteins translocation CT559 lipoprotein Jgi|4377170|gb|AAD18992.1|Outer Membrane Protein Bgi|3329169|gb|AAC68308.1|Outer Membrane Protein Analog CT713gi|4377177|gb|AAD18998.1|Flagellar M-Ring Proteingi|3329175|gb|AAC68314.1|Flagellar M-Ring Proteingi|4377182|gb|AAD19003.1|CT724 hypothetical proteingi|3329181|gb|AAC68319.1|hypothetical proteingi|4377184|gb|AAD19005.1|Rod Shape Protein gi|3329183|gb|AAC68321.1|RodShape Protein gi|4377193|gb|AAD19013.1|CT734 hypothetical proteingi|3329192|gb|AAC68329.1|hypothetical proteingi|4377206|gb|AAD19025.1|CHLTR possible phosphoproteingi|3329204|gb|AAC68339.1|CHLTR possible phosphoproteingi|4377222|gb|AAD19040.1|Muramidase (invasin repeat family)gi|3329221|gb|AAC68354.1|Muramidase (invasin repeat family) CT759gi|4377223|gb|AAD19041.1|Cell Division Protein FtsWgi|3329222|gb|AAC68355.1|Cell Division Protein FtsWgi|4377224|gb|AAD19042.1|Peptidoglycan Transferasegi|3329223|gb|AAC68356.1|Peptidoglycan Transferase CT761gi|4377225|gb|AAD19043.1|Muramate-Ala Ligase & D-Ala-D-gi|3329224|gb|AAC68357.1|UDP-N-acetylmuramate-alanine Ala Ligase ligasegi|4377248|gb|AAD19064.1|Thioredoxin Disulfide Isomerasegi|3329244|gb|AAC68375.1|Thioredoxin Disulfide Isomerasegi|4377261|gb|AAD19076.1|CT788 hypothetical protein -gi|3329253|gb|AAC68383.1|{leader (60) peptide-periplasmic} {leaderpeptide-periplasmi gi|4377280|gb|AAD19093.1|Insulinase family/ProteaseIII gi|3329273|gb|AAC68402.1|Insulinase family/Protease IIIgi|4377287|gb|AAD19099.1|Putative Outer Membrane Proteingi|3329279|gb|AAC68408.1|Putative Outer Membrane Protein D D Familygi|4377306|gb|AAD19116.1|DO Serine Protease gi|3329293|gb|AAC68420.1|DOSerine Protease CT823 gi|4377342|gb|AAD19149.1|ABC transporter permeasegi|3329327|gb|AAC68451.1|ABC transporter permease - pyrimidinebiosynthesis protein gi|4377347|gb|AAD19153.1|CT858 hypothetical proteingi|6578118|gb|AAC68456.2|predicted Protease containing IRBP and DHRdomains gi|4377353|gb|AAD19159.1|CT863 hypothetical proteingi|3329337|gb|AAC68461.1|hypothetical proteingi|4377367|gb|AAD19171.1|Predicted OMPgi|3328795|gb|AAC67967.1|hypothetical proteingi|4377408|gb|AAD19209.1|hypothetical proteingi|3328795|gb|AAC67967.1|hypothetical proteingi|4377409|gb|AAD19210.1|Predicted Outer Membrane Proteingi|3328795|gb|AAC67967.1|hypothetical protein (CT371) gi|4376411|gb|gi|3328512|gb|AAC67705.1|hypothetical protein CT114 gi|4376508|gb|gi|3328585|gb|AAC67772.1|hypothetical protein CT181 gi|4376710|gb|gi|3328692|gb|AAC67872.1|NADH (Ubiquinone) CT279 Oxidoreductase, Gammagi|4376777|gb| gi|3328815|gb|AAC67986.1|hypothetical protein CT389gi|4376782|gb| gi|3328817|gb|AAC67988.1|hypothetical protein CT391gi|4376863|gb| gi|3328887|gb|AAC68054.1|Arginyl tRNA transferase CT454gi|4376866|gb| gi|3328889|gb|AAC68056.1|hypothetical protein CT456gi|4376972|gb| gi|3328991|gb|AAC68153.1|D-Ala-D-Ala CarboxypeptidaseCT551 gi|4377139|gb| gi|3329001|gb|AAC68162.1|hypothetical protein CT560gi|4377154|gb| gi|3329154|gb|AAC68295.1|hypothetical protein CT700

SEQUENCE LISTING SEQ ID NO: 1 - CT733 nucleotide sequenceATGTTAATAAACTTTACCTTTCGCAACTGTCTTTTGTTCCTTGTCACACTGTCTAGTGTCCCTGTTTTCTCAGCACCTCAACCTCGCGGAACGCTTCCTAGCTCGACCACAAAAATTGGATCAGAAGTTTGGATTGAACAAAAAGTCCGCCAATATCCAGAGCTTTTATGGTTAGTAGAGCCGTCCTCTACGGGAGCCTCTTTAAAATCTCCTTCAGGAGCCATCTTTTCTCCAACATTATTCCAAAAAAAGGTCCCTGCTTTCGATATCGCAGTGCGCAGTTTGATTCACTTACATTTATTAATCCAGGGTTCCCGCCAAGCCTATGCTCAACTGATCCAACTACAGACCAGCGAATCCCCTCTAACATTTAAGCAATTCCTTGCATTGCATAAGCAATTAACTCTATTTTTAAATTCCCCTAAGGAATTTTATGACTCTGTTAAAGTGTTAGAGACAGCTATCGTCTTACGTCACTTAGGCTGTTCAACTAAGGCTGTTGCTGCGTTTAAACCTTATTTCTCAGAAATGCAAAGAGAGGCTTTTTACACTAAGGCTCTGCATGTACTACACACCTTCCCAGAGCTAAGCCCATCATTTGCTCGCCTCTCTCCGGAGCAGAAAACTCTCTTCTTCTCCTTGAGAAAATTGGCGAATTACGATGAGTTACTCTCGCTGACGAACACCCCAAGTTTTCAGCTTCTGTCTGCTGGGCGCTCGCAACGAGCTCTTTTAGCTCTGGACTTGTACCTCTATGCTTTGGATTCCTGTGGAGAACAGGGGATGTCCTCTCAATTCCACACAAACTTCGCACCTCTACAGTCCATGTTGCAACAATACGCTACTGTAGAAGAGGCCTTTTCTCGTTATTTTACTTACCGAGCTAATCGATTAGGATTTGATGGCTCTTCTCGATCCGAGATGGCTTTAGTAAGAATGGCCACCTTGATGAACTTGTCTCCTTCCGAAGCTGCGATTTTAACCACAAGCTTCAAAACCCTTCCTACAGAAGAAGCGGATACTTTGATCAATAGTTTCTATACCAATAAGGGCGATTCGTTGGCTCTTTCTCTGCGAGGGTTGCCTACACTTGTATCCGAACTGACGCGAACTGCCCATGGCAATACCAATGCAGAAGCTCGATCTCAGCAAATTTATGCAACTACCCTATCGCTAGTAGTAAAGAGTCTGAAAGCGCACAAAGAAATGCTAAACAAGCAAATTCTTTCTAAGGAAATTGTTTTAGATTTCTCAGAAACTGCAGCTTCTTGCCAAGGATTGGATATCTTTTCCGAGAATGTCGCTGTTCAAATTCACTTAAATGGAACCGTTAGTATCCATTTATAASEQ ID NO: 2 - CT733 protein sequenceMLINFTFRNCLLFLVTLSSVPVFSAPQPRGTLPSSTTKIGSEVWIEQKVRQYPELLWLVEPSSTGASLKSPSGAIFSPTLFQKKVPAFDIAVRSLIHLHLLIQGSRQAYAQLIQLQTSESPLTFKQFLALHKQLTLFLNSPKEFYDSVKVLETAIVLRHLGCSTKAVAAFKPYFSEMQREAFYTKALHVLHTFPELSPSFARLSPEQKTLFFSLRKLANYDELLSLTNTPSFQLLSAGRSQRALLALDLYLYALDSCGEQGMSSQFHTNFAPLQSMLQQYATVEEAFSRYFTYRANRLGFDGSSRSEMALVRMATLMNLSPSEAAILTTSFKTLPTEEADTLINSFYTNKGDSLALSLRGLPTLVSELTRTAHGNTNAEARSQQIYATTLSLVVKSLKAHKEMLNKQILSKEIVLDFSETAASCQGLDIFSENVAVQIHLNGTVSIHLSEQ ID NO: 3 - CT153 nucleotide sequenceATGACTAAGCCTTCTTTCTTATACGTTATTCAACCTTTTTCCGTATTTAATCCACGATTAGGACGTTTCTCTACAGACTCAGATACTTATATCGAAGAAGAAAACCGCCTAGCATCGTTCATTGAGAGTTTGCCACTGGAGATCTTCGATATACCTTCTTTCATGGAAACCGCGATTTCCAATAGCCCCTATATTTTATCTTGGGAGACAACTAAAGACGGCGCTCTGTTCACTATTCTTGAACCCAAACTCTCAGCTTGCGCAGCCACTTGCCTGGTAGCCCCTTCTATACAAATGAAATCCGATGCGGAGCTCCTAGAAGAAATTAAGCAAGCGTTATTACGCAGCTCTCATGACGGTGTGAAATATCGCATCACCAGAGAATCCTTCTCTCCAGAAAAGAAAACTCCTAAGGTTGCTCTAGTCGATGACGATATTGAATTGATTCGCAATGTCGACTTTTTGGGTAGAGCTGTTGACATTGTCAAATTAGACCCTATTAATATTCTGAATACCGTAAGCGAAGAGAATATTCTAGATTACTCTTTTACAAGAGAAACGGCTCAGCTGAGCGCGGATGGTCGTTTTGGTATTCCTCCAGGGACTAAGCTATTCCCTAAACCTTCTTTTGATGTAGAAATCAGTACCTCCATTTTCGAAGAAACAACTTCATTTACTCGAAGTTTTTCTGCATCGGTTACTTTTAGTGTACCAGACCTCGCGGCGACTATGCCTCTTCAAAGCCCTCCCATGGTAGAAAATGGTCAAAAAGAAATTTGTGTCATTCAAAAACACTTATTCCCAAGCTACTCTCCTAAACTAGTCGATATTGTTAAACGATACAAAAGAGAGGCTAAGATCTTGATTAACAAGCTTGCCTTTGGAATGTTATGGCGACATCGGGCTAAAAGCCAAATCCTCACCGAGGGAAGCGTACGTCTAGACTTACAAGGATTCACAGAATCGAAGTACAATTACCAGATTCAAGTAGGATCCCATACGATTGCAGCTGTATTAATCGATATGGATATTTCCAAGATTCAATCCAAATCAGAACAAGCTTATGCAATTAGGAAAATCAAATCAGGCTTTCAACGTAGCTTGGATGACTATCATATTTATCAAATTGAAAGAAAACAAACCTTTTCTTTTTCTCCGAAGCATCGCAGCCTCTCATCCACATCCCATTCCGAAGATTCTGATTTGGATCTTTCTGAAGCAGCCGCCTTTTCAGGAAGTCTTACCTGCGAGTTTGTAAAAAAAAGCACTCAACATGCCAAGAATACCGTCACATGTTCCACAGCCGCTCATTCCCTATACACACTCAAAGAAGATGACAGCTCGAACCCCTCTGAAAAACGATTAGATAGTTGTTTCCGCAATTGGATTGAAAACAAACTAAGCGCCAATTCTCCAGATTCCTGGTCAGCGTTTATTCAAAAATTCGGAACACACTATATTGCATCAGCAACTTTTGGAGGGATAGGTTTCCAAGTGCTCAAACTATCTTTTGAACAGGTGGAGGATCTACATAGCAAAAAGATCTCCTTAGAAACCGCAGCAGCCAACTCTCTATTAAAAGGTTCTGTATCCAGCAGCACAGAATCTGGATACTCCAGCTATAGCTCCACGTCTTCTTCTCATACGGTATTTTTAGGAGGAACGGTCTTACCTTCGGTTCATGATGAACGTTTAGACTTTAAAGATTGGTCGGAAAGTGTGCACCTGGAACCTGTTCCTATCCAGGTTTCTTTACAACCTATAACGAATTTACTAGTTCCTCTCCATTTTCCTAATATCGGTGCTGCAGAGCTCTCTAATAAACGAGAATCTCTTCAACAAGCGATTCGAGTCTATCTCAAAGAACATAAAGTAGATGAGCAAGGAGAACGTACTACATTTACATCAGGAATCGATAATCCTTCTTCCTGGTTTACCTTAGAAGCTGCCCACTCTCCTCTTATAGTCAGTACTCCTTACATTGCTTCGTGGTCTACGCTTCCTTATTTGTTCCCAACATTAAGAGAACGTTCTTCGGCAACCCCTATCGTTTTCTATTTTTGTGTAGATAATAATGAACATGCTTCGCAAAAAATATTAAACCAATCGTATTGCTTCCTCGGGTCCTTGCCTATTCGACAAAAAATTTTTGGTAGCGAATTTGCTAGTTTCCCCTATCTATCTTTCTATGGAAATGCAAAAGAGGCGTACTTTGATAACACGTACTACCCAACGCGTTGTGGGTGGATTGTTGAAAAGTTAAATACTACACAAGATCAATTCCTCCGGGATGGAGACGAGGTGCGACTAAAACATGTTTCCAGCGGAAAGTATCTAGCAACAACTCCTCTTAAGGATACCCATGGTACACTCACGCGTACAACGAACTGTGAAGATGCTATCTTTATTATTAAAAAATCTTCAGGTTATTGASEQ ID NO: 4 - CT153 protein sequenceMTKPSFLYVIQPFSVFNPRLGRFSTDSDTYIEEENRLASFIESLPLEIFDIPSFMETAISNSPYILSWETTKDGALFTILEPKLSACAATCLVAPSIQMKSDAELLEEIKQALLRSSHDGVKYRITRESFSPEKKTPKVALVDDDIELIRNVDFLGRAVDIVKLDPINILNTVSEENILDYSFTRETAQLSADGRFGIPPGTKLFPKPSFDVEISTSIFEETTSFTRSFSASVTFSVPDLAATMPLQSPPMVENGQKEICVIQKHLFPSYSPKLVDIVKRYKREAKILINKLAFGMLWRHRAKSQILTEGSVRLDLQGFTESKYNYQIQVGSHTIAAVLIDMDISKIQSKSEQAYAIRKIKSGFQRSLDDYHIYQIERKQTFSFSPKHRSLSSTSHSEDSDLDLSEAAAFSGSLTCEFVKKSTQHAKNTVTCSTAAHSLYTLKEDDSSNPSEKRLDSCFRNWIENKLSANSPDSWSAFIQKFGTHYIASATFGGIGFQVLKLSFEQVEDLHSKKISLETAAANSLLKGSVSSSTESGYSSYSSTSSSHTVFLGGIVLPSVHDERLDFKDWSESVHLEPVPIQVSLQPITNLLVPLHFPNIGAAELSNKRESLQQAIRVYLKEHKVDEQGERTTFTSGIDNPSSWFTLEAAHSPLIVSTPYIASWSTLPYLFPTLRERSSATPIVFYFCVDNNEHASQKILNQSYCFLGSLPIRQKIFGSEFASFPYLSFYGNAKEAYFDNTYYPTRCGWIVEKLNTTQDQFLRDGDEVRLKHVSSGKYLATTPLKDTHGTLTRTTNCEDAIFIIKKSSGYSEQ ID NO: 5 - CT601 nucleotide sequenceATGCTCGCTAATCGCTTATTCTTAATAACCCTTTTAGGGTTAAGTTCGTCTGTTTACGGCGCAGGTAAAGCACCGTCTTTGCAGGCTATTCTAGCCGAAGTCGAAGACACCTCCTCTCGTCTACACGCTCATCACAATGAGCTTGCTATGATCTCTGAACGCCTCGATGAGCAAGACACGAAACTACAGCAACTTTCGTCAACACAAGATCATAACCTACCTCGACAAGTTCAGCGACTAGAAACGGACCAAAAAGCTTTGGCAAAAACACTGGCGATTCTTTCGCAATCCGTCCAAGATATTCGGTCTTCTGTACAAAATAAATTACAAGAAATCCAACAAGAACAAAAAAAATTAGCACAAAATTTGCGAGCGCTTCGTAACTCTTTACAAGCTCTCGTTGATGGCTCTTCTCCAGAAAATTATATTGATTTCCTAACTGGTGAAACCCCGGAACATATTCATATTGTTAAACAAGGAGAGACCCTGAGCAAGATCGCGAGTAAATATAACATCCCCGTCGTAGAATTAAAAAAACTTAATAAACTAAATTCGGATACTATTTTTACAGATCAAAGAATTCGCCTTCCGAAAAAGAAATAGSEQ ID NO: 6 - CT601 protein sequenceMLANRLFLITLLGLSSSVYGAGKAPSLQAILAEVEDTSSRLHAHHNELAMISERLDEQDTKLQQLSSTQDHNLPRQVQRLETDQKALAKTLAILSQSVQDIRSSVQNKLQEIQQEQKKLAQNLRALRNSLQALVDGSSPENYIDFLTGETPEHIHIVKQGETLSKIASKYNIPVVELKKLNKLNSDTIFTDQRIRLPKKKSEQ ID NO: 7 - CT279 nucleotide sequenceATGGCATCCAAGTCTCGCCATTATCTTAATCAGCCTTGGTACATTATCTTATTCATCTTTGTTCTTAGTTTAATTGCTGGTACCCTCCTGTCTTCTGTGTATTATGTCCTTGCACCTATCCAACAGCAAGCTGCGGAATTCGATCGCAATCAACAAATGCTAATGGCTGCACAAGTAATTTCTTCCGATAACACATTCCAAGTCTATGAAAAGGGAGATTGGCACCCAGCCCTATATAATACTAAAAAGCAGTTGCTAGAGATCTCCTCTACTCCTCCTAAAGTAACCGTGACAACTTTAAGCTCATATTTTCAAAACTTTGTTAGAGTCTTGCTTACAGATACACAAGGAAATCTTTCTTCATTCGAAGACCATAATCTCAATCTAGAAGAATTTTTATCTCAACCAACTCCTGTAATACATGGTCTTGCCCTTTATGTGGTCTACGCTATCCTACACAACGATGCAGCTTCCTCTAAATTATCTGCTTCCCAAGTAGCGAAAAATCCAACAGCTATAGAATCTATAGTTCTTCCTATAGAAGGTTTTGGTTTGTGGGGACCTATCTATGGATTCCTTGCTCTAGAAAAAGACGGGAATACTGTTCTTGGTACTTCTTGGTATCAACATGGCGAGACTCCTGGATTAGGAGCAAATATCGCTAACCCTCAATGGCAAAAAAATTTCAGAGGCAAAAAAGTATTTCTAGTCTCAGCTTCTGGAGAAACAGATTTTGCTAAGACAACCCTAGGACTGGAAGTTATAAAAGGATCTGTATCTGCAGCATTAGGAGACTCACCTAAAGCTGCTTCTTCCATCGACGGAATTTCAGGAGCTACTTTGACTTGTAATGGTGTTACCGAATCCTTCTCTCATTCTCTAGCTCCCTACCGCGCTTTGTTGACTTTCTTCGCCAACTCTAAACCTAGTGGAGAGTCTCATGACCACTAA SEQ ID NO: 8 - CT279 protein sequenceMASKSRHYLNQPWYIILFIFVLSLIAGTLLSSVYYVLAPIQQQAAEFDRNQQMLMAAQVISSDNTFQVYEKGDWHPALYNTKKQLLEISSTPPKVTVTTLSSYFQNFVRVLLTDTQGNLSSFEDHNLNLEEFLSQPTPVIHGLALYVVYAILHNDAASSKLSASQVAKNPTAIESIVLPIEGFGLWGPIYGFLALEKDGNTVLGTSWYQHGETPGLGANIANPQWQKNFRGKKVFLVSASGETDFAKTTLGLEVIKGSVSAALGDSPKAASSIDGISGATLTCNGVTESFSHSLAPYRALLTFFANSKPSGESHDH SEQ ID NO: 9 - CT443 nucleotide sequenceATGCGAATAGGAGATCCTATGAACAAACTCATCAGACGAGCAGTGACGATCTTCGCGGTGACTAGTGTGGCGAGTTTATTTGCTAGCGGGGTGTTAGAGACCTCTATGGCAGAGTCTCTCTCTACAAACGTTATTAGCTTAGCTGACACCAAAGCGAAAGACAACACTTCTCATAAAAGCAAAAAAGCAAGAAAAAACCACAGCAAAGAGACTCCCGTAGACCGTAAAGAGGTTGCTCCGGTTCATGAGTCTAAAGCTACAGGACCTAAACAGGATTCTTGCTTTGGCAGAATGTATACAGTCAAAGTTAATGATGATCGCAATGTTGAAATCACACAAGCTGTTCCTGAATATGCTACGGTAGGATCTCCCTATCCTATTGAAATTACTGCTACAGGTAAAAGGGATTGTGTTGATGTTATCATTACTCAGCAATTACCATGTGAAGCAGAGTTCGTACGCAGTGATCCAGCGACAACTCCTACTGCTGATGGTAAGCTAGTTTGGAAAATTGACCGCTTAGGACAAGGCGAAAAGAGTAAAATTACTGTATGGGTAAAACCTCTTAAAGAAGGTTGCTGCTTTACAGCTGCAACAGTATGCGCTTGTCCAGAGATCCGTTCGGTTACAAAATGTGGACAACCTGCTATCTGTGTTAAACAAGAAGGCCCAGAGAATGCTTGTTTGCGTTGCCCAGTAGTTTACAAAATTAATATAGTGAACCAAGGAACAGCAACAGCTCGTAACGTTGTTGTTGAAAATCCTGTTCCAGATGGTTACGCTCATTCTTCTGGACAGCGTGTACTGACGTTTACTCTTGGAGATATGCAACCTGGAGAGCACAGAACAATTACTGTAGAGTTTTGTCCGCTTAAACGTGGTCGTGCTACCAATATAGCAACGGTTTCTTACTGTGGAGGACATAAAAATACAGCAAGCGTAACAACTGTGATCAACGAGCCTTGCGTACAAGTAAGTATTGCAGGAGCAGATTGGTCTTATGTTTGTAAGCCTGTAGAATATGTGATCTCCGTTTCCAATCCTGGAGATCTTGTGTTGCGAGATGTCGTCGTTGAAGACACTCTTTCTCCCGGAGTCACAGTTCTTGAAGCTGCAGGAGCTCAAATTTCTTGTAATAAAGTAGTTTGGACTGTGAAAGAACTGAATCCTGGAGAGTCTCTACAGTATAAAGTTCTAGTAAGAGCACAAACTCCTGGACAATTCACAAATAATGTTGTTGTGAAGAGCTGCTCTGACTGTGGTACTTGTACTTCTTGCGCAGAAGCGACAACTTACTGGAAAGGAGTTGCTGCTACTCATATGTGCGTAGTAGATACTTGTGACCCTGTTTGTGTAGGAGAAAATACTGTTTACCGTATTTGTGTCACCAACAGAGGTTCTGCAGAAGATACAAATGTTTCTTTAATGCTTAAATTCTCTAAAGAACTGCAACCTGTATCCTTCTCTGGACCAACTAAAGGAACGATTACAGGCAATACAGTAGTATTCGATTCGTTACCTAGATTAGGTTCTAAAGAAACTGTAGAGTTTTCTGTAACATTGAAAGCAGTATCAGCTGGAGATGCTCGTGGGGAAGCGATTCTTTCTTCCGATACATTGACTGTTCCAGTTTCTGATACAGAGAATACACACATCTATTAASEQ ID NO: 10 - CT443 protein sequenceMRIGDPMNKLIRRAVTIFAVTSVASLFASGVLETSMAESLSTNVISLADTKAKDNTSHKSKKARKNHSKETPVDRKEVAPVHESKATGPKQDSCFGRMYTVKVNDDRNVEITQAVPEYATVGSPYPIEITATGKRDCVDVIITQQLPCEAEFVRSDPATTPTADGKLVWKIDRLGQGEKSKITVWVKPLKEGCCFTAATVCACPEIRSVTKCGQPAICVKQEGPENACLRCPVVYKINIVNQGTATARNVVVENPVPDGYAHSSGQRVLIFTLGDMQPGEHRTITVEFCPLKRGRATNIATVSYCGGHKNTASVTTVINEPCVQVSIAGADWSYVCKPVEYVISVSNPGDLVLRDVVVEDTLSPGVTVLEAAGAQISCNKVVWTVKELNPGESLQYKVLVRAQTPGQFTNNVVVKSCSDCGTCTSCAEATTYWKGVAATHMCVVDTCDPVCVGENTVYRICVTNRGSAEDTNVSLMLKFSKELQPVSFSGPTKGTITGNTVVFDSLPRLGSKETVEFSVTLKAVSAGDARGEAILSSDTLTVPVSDTENTHIY SEQ ID NO: 11 - CT372 nucleotide sequenceATGCAGGCTGCACACCATCACTATCACCGCTACACAGATAAACTGCACAGACAAAACCATAAAAAAGATCTCATCTCTCCCAAACCTACCGAACAAGAGGCGTGCAATACTTCTTCCCTTAGTAAGGAATTAATCCCTCTATCAGAACAAAGAGGCCTTTTATCCCCCATCTGTGACTTTATTTCGGAACGCCCTTGCTTACACGGAGTTTCTGTTAGAAATCTCAAGCAAGCGCTAAAAAATTCTGCAGGAACCCAAATTGCACTGGATTGGTCTATTCTCCCTCAATGGTTCAATCCTCGGGTCTCTCATGCCCCTAAGCTTTCTATCCGAGACTTTGGGTATAGCGCACACCAAACTGTTACCGAAGCCACTCCTCCTTGCTGGCAAAACTGCTTTAATCCATCTGCGGCCGTTACTATCTATGATTCCTCATATGGGAAAGGGGTCTTTCAAATATCCTATACCCTTGTCCGCTATTGGAGAGAGAATGCTGCGACTGCTGGCGATGCTATGATGCTCGCAGGGAGTATCAATGATTATCCCTCTCGTCAGAACATTTTCTCTCAGTTTACTTTCTCCCAAAACTTCCCAAATGAACGGGTGAGTCTGACAATTGGTCAGTACTCACTCTATGCAATAGACGGAACATTATACAATAACGATCAACAACTTGGATTCATTAGTTACGCATTATCACAAAATCCAACAGCAACTTATTCCTCTGGAAGTCTTGGAGCTTACCTACAAGTCGCTCCTACCGCAAGCACAAGTCTTCAAATAGGATTTCAAGACGCTTATAATATCTCCGGATCCTCTATCAAATGGAGTAACCTTACAAAAAATAGATACAATTTTCACGGTTTTGCTTCCTGGGCTCCCCGCTGTTGCTTAGGATCTGGCCAGTACTCCGTGCTTCTTTATGTGACTAGACAAGTTCCAGAACAGATGGAACAAACAATGGGATGGTCAGTCAATGCGAGTCAACACATATCTTCTAAACTGTATGTGTTTGGAAGATACAGCGGTGTTACAGGACATGTGTTCCCGATTAACCGCACGTATTCATTCGGTATGGCCTCTGCAAATTTATTTAACCGTAACCCACAAGATTTATTTGGAATTGCTTGCGCATTCAATAATGTACACCTCTCTGCTTCTCCAAATACTAAAAGAAAATACGAAACTGTAATCGAAGGGTTTGCAACTATCGGTTGCGGCCCCTATCTTTCTTTCGCTCCAGACTTCCAACTCTACCTCTACCCAGCTCTTCGTCCAAACAAACAATCTGCCCGTGTTTATAGCGTGCGAGCTAATTTAGCTATCTAA SEQ ID NO: 12 - CT372 protein sequenceMQAAHHHYHRYTDKLHRQNHKKDLISPKPTEQEACNTSSLSKELIPLSEQRGLLSPICDFISERPCLHGVSVRNLKQALKNSAGTQIALDWSILPQWFNPRVSHAPKLSIRDFGYSAHQTVTEATPPCWQNCFNPSAAVTIYDSSYGKGVFQISYTLVRYWRENAATAGDAMMLAGSINDYPSRQNIFSQFTFSQNFPNERVSLTIGQYSLYAIDGTLYNNDQQLGFISYALSQNPTATYSSGSLGAYLQVAPTASTSLQIGFQDAYNISGSSIKWSNLTKNRYNFHGFASWAPRCCLGSGQYSVLLYVTRQVPEQMEQTMGWSVNASQHISSKLYVFGRYSGVTGHVFPINRTYSFGMASANLFNRNPQDLFGIACAFNNVHLSASPNTKRKYETVIEGFATIGCGPYLSFAPDFQLYLYPALRPNKQSARVYSVRANLAISEQ ID NO: 13 - CT456 nucleotide sequenceATGACGAATTCTATATCAGGTTATCAACCTACTGTTACAACTTCTACATCATCAACCACTTCGGCATCAGGTGCTTCCGGATCTCTGGGAGCTTCTTCTGTATCTACTACCGCAAACGCTACAGTTACACAAACAGCAAACGCAACAAATTCAGCGGCTACATCTTCTATCCAAACGACTGGAGAGACTGTAGTAAACTATACGAATTCAGCCTCCGCCCCCAATGTAACTGTATCGACCTCCTCTTCTTCCACACAAGCCACAGCCACTTCGAATAAAACTTCCCAAGCCGTTGCTGGAAAAATCACTTCTCCAGATACTTCAGAAAGCTCAGAAACTAGCTCTACCTCATCAAGCGATCATATCCCTAGCGATTACGATGACGTTGGTAGCAATAGTGGAGATATTAGCAACAACTACGATGACGTAGGTAGTAACAACGGAGATATCAGTAGCAATTATGACGATGCTGCTGCTGATTACGAGCCGATAAGAACTACTGAAAATATTTATGAGAGTATTGGTGGCTCTAGAACAAGTGGCCCAGAAAATACAAGTGGTGGTGCAGCAGCAGCACTCAATTCTCTAAGAGGCTCCTCCTACAGCAATTATGACGATGCTGCTGCTGATTACGAGCCGATAAGAACTACTGAAAATATTTATGAGAGTATTGGTGGCTCTAGAACAAGTGGCCCAGAAAATACGAGTGGTGGTGCAGCAGCAGCACTCAATTCTCTAAGAGGCTCCTCCTACAGCAATTATGACGATGCTGCTGCTGATTACGAGCCGATAAGAACTACTGAAAATATTTATGAGAGTATTGGTGGCTCTAGAACAAGTGGCCCAGAAAATACGAGTGATGGTGCAGCAGCAGCAGCACTCAATTCTCTAAGAGGCTCCTCCTACACAACAGGGCCTCGTAACGAGGGTGTATTCGGCCCTGGACCGGAAGGACTACCAGACATGTCTCTTCCTTCATACGATCCTACAAATAAAACCTCGTTATTGACTTTCCTCTCCAACCCTCATGTAAAGTCGAAAATGCTTGAAAACTCGGGGCATTTCGTCTTCATTGATACAGATAGAAGTAGTTTCATTCTTGTTCCTAACGGAAATTGGGACCAAGTCTGTTCAATTAAAGTTCAAAATGGAAAGACCAAAGAAGATCTCGACATCAAAGACTTGGAAAACATGTGTGCAAAATTCTGTACAGGGTTTAGCAAATTCTCTGGTGACTGGGACAGTCTTGTAGAACCTATGGTGTCAGCCAAAGCTGGAGTGGCCAGCGGAGGCAATCTTCCCAATACAGTGATTATCAATAATAAATTCAAAACTTGCGTTGCTTATGGTCCTTGGAATAGCCAGGAAGCAAGTTCTGGTTATACACCTTCTGCTTGGAGACGTGGTCATCGAGTAGATTTTGGAGGAATTTTTGAGAAAGCCAACGACTTTAATAAAATCAACTGGGGAACTCAAGCCGGGCCTAGTAGCGAAGACGATGGCATTTCCTTCTCCAATGAAACTCCTGGAGCTGGTCCTGCAGCTGCTCCATCACCAACGCCATCCTCTATTCCTATCATCAATGTCAATGTCAATGTTGGCGGAACTAATGTGAATATTGGAGATACGAATGTCAACACGACTAACACCACACCAACAACTCAATCTACAGACGCCTCTACAGATACAAGCGATATCGATGACATAAATACCAACAACCAAACTGATGATATCAATACGACAGACAAAGACTCTGACGGAGCTGGTGGAGTCAATGGCGATATATCCGAAACAGAATCCTCTTCTGGAGATGATTCAGGAAGTGTCTCTTCCTCAGAATCAGACAAGAATGCCTCTGTCGGAAATGACGGACCTGCTATGAAAGATATCCTTTCTGCCGTGCGTAAACACCTAGACGTCGTTTACCCTGGCGAAAATGGCGGTTCTACAGAAGGGCCTCTCCCAGCTAACCAAACTCTCGGAGACGTAATCTCTGATGTAGAGAATAAAGGCTCCGCTCAGGATACAAAATTGTCAGGAAATACAGGAGCTGGGGATGACGATCCAACAACCACAGCTGCTGTAGGTAATGGAGCGGAAGAGATCACTCTTTCCGACACAGATTCTGGTATCGGAGATGATGTATCCGATACAGCGTCTTCATCTGGGGATGAATCCGGAGGAGTCTCCTCTCCCTCTTCAGAATCCAATAAAAATACTGCCGTTGGAAATGACGGACCTTCTGGACTAGATATCCTCGCTGCCGTACGTAAACATTTAGATAAGGTTTACCCTGGCGACAATGGTGGTTCTACAGAAGGGCCTCTCCAAGCTAACCAAACTCTTGGAGATATCGTCCAGGATATGGAAACAACAGGGACATCCCAAGAAACCGTTGTATCCCCATGGAAAGGAAGCACTTCTTCAACGGAATCAGCAGGAGGAAGTGGTAGCGTACAAACACTACTGCCTTCACCACCTCCAACCCCGTCAACTACAACATTAAGAACGGGCACAGGAGCTACCACCACATCCTTGATGATGGGAGGACCAATCAAAGCTGACATAATAACAACTGGTGGCGGAGGACGAATTCCTGGAGGAGGAACGTTAGAAAAGCTGCTCCCTCGTATACGTGCGCACTTAGACATATCCTTTGATGCGCAAGGCGATCTCGTAAGTACTGAAGAGCCTCAGCTTGGCTCGATTGTAAACAAATTCCGCCAAGAAACTGGTTCAAGAGGAATCTTAGCTTTCGTTGAGAGTGCTCCAGGCAAGCCGGGATCTGCACAGGTCTTAACGGGTACAGGGGGAGATAAAGGCAACCTATTCCAAGCAGCTGCCGCAGTCACCCAAGCCTTAGGAAATGTTGCAGGGAAAGTCAACCTTGCGATACAAGGCCAAAAACTATCATCCCTAGTCAATGACGACGGGAAGGGGTCTGTTGGAAGAGATTTATTCCAAGCAGCAGCCCAAACAACTCAAGTGCTAAGCGCACTGATTGATACCGTAGGATAA SEQ ID NO: 14 - CT456 protein sequenceMTNSISGYQPTVTTSTSSTTSASGASGSLGASSVSTTANATVTQTANATNSAATSSIQTTGETVVNYTNSASAPNVTVSTSSSSTQATATSNKTSQAVAGKITSPDTSESSETSSTSSSDHIPSDYDDVGSNSGDISNNYDDVGSNNGDISSNYDDAAADYEPIRTTENIYESIGGSRTSGPENTSGGAAAALNSLRGSSYSNYDDAAADYEPIRTTENIYESIGGSRTSGPENTSGGAAAALNSLRGSSYSNYDDAAADYEPIRTTENIYESIGGSRTSGPENTSDGAAAAALNSLRGSSYTTGPRNEGVFGPGPEGLPDMSLPSYDPTNKTSLLTFLSNPHVKSKMLENSGHFVFIDTDRSSFILVPNGNWDQVCSIKVQNGKTKEDLDIKDLENMCAKFCTGFSKFSGDWDSLVEPMVSAKAGVASGGNLPNTVIINNKFKTCVAYGPWNSQEASSGYTPSAWRRGHRVDFGGIFEKANDFNKINWGTQAGPSSEDDGISFSNETPGAGPAAAPSPTPSSIPIINVNVNVGGTNVNIGDTNVNTTNTTPTTQSTDASTDTSDIDDINTNNQTDDINTTDKDSDGAGGVNGDISETESSSGDDSGSVSSSESDKNASVGNDGPAMKDILSAVRKHLDVVYPGENGGSTEGPLPANQTLGDVISDVENKGSAQDTKLSGNTGAGDDDPTTTAAVGNGAEEITLSDTDSGIGDDVSDTASSSGDESGGVSSPSSESNKNTAVGNDGPSGLDILAAVRKHLDKVYPGDNGGSTEGPLQANQTLGDIVQDMETTGTSQETVVSPWKGSTSSTESAGGSGSVQTLLPSPPPTPSTTTLRTGTGATTTSLMMGGPIKADIITTGGGGRIPGGGTLEKLLPRIRAHLDISFDAQGDLVSTEEPQLGSIVNKFRQETGSRGILAFVESAPGKPGSAQVLTGTGGDKGNLFQAAAAVTQALGNVAGKVNLAIQGQKLSSLVNDDGKGSVGRDLFQAAAQTTQVLSALIDTVG SEQ ID NO: 15: CT381 nucleotide sequenceATGTGCATAAAAAGAAAAAAAACATGGATAGCTTTTTTAGCAGTTGTCTGTAGTTTTTGTTTGACGGGTTGTTTAAAAGAAGGGGGAGACTCCAATAGTGAAAAATTTATTGTAGGGACTAATGCAACCTACCCTCCTTTTGAGTTTGTTGATAAGCGAGGAGAGGTTGTAGGCTTCGATATAGACTTGGCTAGAGAGATTAGTAACAAGCTGGGGAAAACGCTGGACGTTCGGGAGTTTTCCTTTGATGCACTCATTCTAAACCTAAAACAGCATCGGATTGATGCGGTTATAACAGGGATGTCCATTACTCCTTCTAGATTGAAGGAAATTCTTATGATTCCCTATTATGGGGAGGAAATAAAACACTTGGTTTTAGTGTTTAAAGGAGAGAATAAGCATCCATTGCCACTCACTCAATATCGTTCTGTAGCTGTTCAAACAGGAACCTATCAAGAGGCCTATTTACAGTCTCTTTCTGAAGTTCATATTCGCTCTTTTGATAGCACTCTAGAAGTACTCATGGAAGTCATGCATGGTAAATCTCCCGTCGCTGTTTTAGAGCCATCTATCGCTCAAGTTGTCTTGAAAGATTTCCCGGCTCTTTCTACAGCAACCATAGATCTCCCTGAAGATCAGTGGGTTTTAGGATACGGGATTGGCGTTGCTTCAGATCGCCCAGCTTTAGCCTTGAAAATCGAGGCAGCTGTGCAAGAGATCCGAAAAGAAGGAGTGCTAGCAGAGTTGGAACAGAAGTGGGGTTTGAACAACTAA SEQ ID NO: 16: CT381 protein sequenceMCIKRKKTWIAFLAVVCSFCLTGCLKEGGDSNSEKFIVGTNATYPPFEFVDKRGEVVGFDIDLAREISNKLGKTLDVREFSFDALILNLKQHRIDAVITGMSITPSRLKEILMIPYYGEEIKHLVLVFKGENKHPLPLTQYRSVAVQTGTYQEAYLQSLSEVHIRSFDSTLEVLMEVMHGKSPVAVLEPSIAQVVLKDFPALSTATIDLPEDQWVLGYGIGVASDRPALALKIEAAVQEIRKEGVLAELEQKWGLNN SEQ ID NO: 17: CT043 nucleotide sequenceATGTCCAGGCAGAATGCTGAGGAAAATCTAAAAAATTTTGCTAAAGAGCTTAAACTCCCCGACGTGGCCTTCGATCAGAATAATACGTGCATTTTGTTTGTTGATGGAGAGTTTTCTCTTCACCTGACCTACGAAGAACACTCTGATCGCCTTTATGTTTACGCACCTCTTCTTGACGGACTGCCAGACAATCCGCAAAGAAGGTTAGCTCTATATGAGAAGTTGTTAGAAGGCTCTATGCTCGGAGGCCAAATGGCTGGTGGAGGGGTAGGAGTCGCTACTAAGGAACAGTTGATCTTAATGCACTGCGTGTTAGACATGAAGTATGCAGAGACCAACCTACTCAAAGCTTTTGCACAGCTTTTTATTGAAACCGTTGTGAAATGGCGAACTGTTTGTTCTGATATCAGCGCTGGACGAGAACCCACTGTTGATACCATGCCACAAATGCCTCAAGGGGGTGGCGGAGGAATTCAACCTCCTCCAGCAGGAATCCGTGCATAASEQ ID NO: 18: CT043 protein sequenceMSRQNAEENLKNFAKELKLPDVAFDQNNTCILFVDGEFSLHLTYEEHSDRLYVYAPLLDGLPDNPQRRLALYEKLLEGSMLGGQMAGGGVGVATKEQLILMHCVLDMKYAETNLLKAFAQLFIETVVKWRTVCSDISAGREPTVDTMPQMPQGGGGGIQPPPAGIRA SEQ ID NO: 19: CT711/hypothetical protein (AAC68306)MSIQPTSISLTKNITAALAGEQVDAAAVYMPQAVFFFQQLDEKSKGLKQALGLLEEVDLEKFIPSLEKSPTPITTGTTSKISADGIEIVGELSSETILADPNKAAAQVFGEGLADSFDDWLRLSENGGIQDPTAIEEEIVTKYQTELNTLRNKLKQQSLTDDEYTKLYAIPQNFVKEIESLKNENNVRLIPKSKVTNFWQNIMLTYNSVTSLSEPVTDAMNTTMAEYSLYIERATEAAKLIREITNTIKDIFNPVWDVREQTGIFGLKGAEYNALEGNMIQSLLSFAGLFRQLMSRTATVDEIGALYPKNDKNEDVIHTAIDDYVNSLADLKANEQVKLNGLLSLVYAYYASTLGFAKKDVFNNAQASFTDYTNFLNQEIQYWTPRETSSFNISNQALQTFKNKPSADYNGVYLFDNKGLETNLFNPTFFFDVVSLMTADPIKTMSRQDYNKVITASESSIQKINQAITAWELAIAECGTKKAKLEPSSLNYFNAMVEAKKTFVETSPIQMVYSSLMLDKYLPNQQYILETLGSQMTFSNKAARYLNDIIAYAVSFQTADVYYSLGMYLRQMNQQEFPEVISRANDTVKKEIDRSRADLFHCKKAIEKIKELVTSVNADTELTSSQRAELLETLASYAFEFENLYHNLSNVYVMVSKVQISGVSKPDEVDEAFTAKIGSKEFDTWIQQLTTFESAVIEGGRNGVMPGGEQQVLQSLESKQQDYTSFNQNQQLALQMESAAIQQEWTMVAAALALMNQIFAKLIRRFKSEQ ID NO: 20: CT114/hypothetical protein (AAC67705)MCFIGIGSLLLPTALRATERMRKEPIPLLDKQQSFWNVDPYCLESICACFVAHRDPLSAKQLMYLFPQLSEEDVSVFARCILSSKRPEYLFSKSEEELFAKLILPRVSLGVHRDDDLARVLVLAEPSAEEQKARYYSLYLDVLALRAYVERERLASAAHGDPERIDLATIEAINTILFQEEGWRYPSKQEMFENRFSELAAVTDSKFGVCLGTVVLYQAVAQRLDLSLDPVTPPGHIYLRYKDKVNIETTSGGRHLPTERYCECIKESQLKVRSQMELIGLTFMNRGAFFLQKGEFLQASLAYEQAQSYLSDEQISDLLGITYVLLGKKAAGEALLKKSAEKTRRGSSIYDYFQGYISPEILGVLFADSGVTYQETLEYRKKLVMLSKKYPKSGSLRLRLATTALELGLVKEGVQLLEESVKDAPEDLSLRLQFCKILCNRHDYVRAKYHFDQAQALLIKEGLFSEKTSYTLLKTIGKKLSLFAPS SEQ ID NO: 21: CT480/oppA_4 (AAC68080)MIDKIIRTILVLSLFLLYWSSDLLEKDVKSIKRELKALHEDVLELVRISHQQKNWVQSTDFSVSPEISVLKDCGDPAFPNLLCEDPYVEKVVPSLLKEGFVPKGILRTAQVGRPDNLSPFNGFVNIVRFYELCVPNLAVEHVGKYEEFAPSLALKIEEHYVEDGSGDKEFHIYLRPNMFWEPIDPTLFPKNITLADSFLRPHPVTAHDVKFYYDVVMNPYVAEMRAVAMRSYFEDMVSVRVENDLKLIVRWRAHTVRNEQGEEEKKVLYSAFANTLALQPLPCFVYQHFANGEKIVPEDSDPDTYRKDSVWAQNFSSHWAYNYIVSCGAFRFAGMDDEKITLVRNPNYHNPFAALVEKRYIYMKDSTDSLFQDFKAGKVDIAYFPPNHVDNLASFMQTSAYKEQAARGEAILEKNSSDRSYSYIGWNCLSLFFNNRSVRQAMNMLIDRDRIIEQCLDGRGVSVSGPFSLCSPSYNRDVEGWQYSPEEAARKLEEEGWIDADGDGIREKVIDGVVVPFRFRLCYYVKSVTARTIAEYVATVCKEVGIECCLLGLDMADYSQALEEKNFDAILSGWCLGTPPEDPRALWHSEGALEKGSANAVGFCNEEADRIIEQLSYEYDSNKRQALYHRFHEVIHEESPYAFLYSRQYSLVYKEFVKNIFVPTEHQDLIPGAQDETVNLSMLWVDKEEGRCSAIS SEQ ID NO: 22: CT089/lcrE (AAC67680)MTASGGAGGLGSTQTVDVARAQAAAATQDAQEVIGSQEASEASMLKGCEDLINPAAATRIKKKGEKFESLEARRKPTADKAEKKSESTEEKGDTPLEDRFTEDLSEVSGEDFRGLKNSFDDDSSPDEILDALTSKFSDPTIKDLALDYLIQTAPSDGKLKSTLIQAKHQLMSQNPQAIVGGRNVLLASETFASRANTSPSSLRSLYFQVTSSPSNCANLHQMLASYLPSEKTAVMEFLVNGMVADLKSEGPSIPPAKLQVYMTELSNLQALHSVNSFFDRNIGNLENSLKHEGHAPIPSLTTGNLIKTFLQLVEDKFPSSSKAQKALNELVGPDTGPQTEVLNLFFRALNGCSPRIFSGAEKKQQLASVITNTLDAINADNEDYPKPGDFPRSSFSSTPPHAPVPQSEIPTSPTSTQPPSPSEQ ID NO: 23: CT734/hypothetical protein (AAC68329)MKKFIYKYSFGALLLLSGLSGLSSCCANSYGSTLAKNTAEIKEESVTLREKPDAGCKKKSSCYLRKFFSRKKPKEKTEPVLPNFKSYADPMTDSERKDLSFVVSAAADKSSIALAMAQGEIKGALSRIREIHPLALLQALAEDPALIAGMKKMQGRDWVWNIFITELSKVFSQAASLGAFSVADVAAFASTLGLDSGTVTSIVDGERWAELIDVVIQNPAISEQ ID NO: 24: CT016/hypothetical protein (AAC67606)MKVKINDQFICISPYISARWNQIAFIESCDGGTEGGITLKLHLIDGETVSIPNLGQAIVDEVFQEHLLYLESTAPQKNKEEEKISSLLGAVQQMAKGCEVQVFSQKGLVSMLLGGAGSINVLLQHSPEHKDHPDLPTDLLERIAQMMRSLSIGPTSILAKPEPHCNCLHCQIGRATVEEEDAGVSDEDLTFRSWDISQSGEKMYTVTDPLNPEEQFNVYLGTPIGCTCGQPYCEHVKAVLYT SEQ ID NO: 25: CM homolog of CT279 = TC_0551ATGGCATCCAAGTCTCGTCATTATCTTAACCAGCCTTGGTACATTATCTTATTCATCTTTGTTCTTAGTCTGGTTGCTGGTACCCTTCTTTCTTCAGTTTCCTATGTTCTATCTCCAATCCAAAAACAAGCTGCAGAATTTGATCGTAATCAGCAAATGTTGATGGCCGCACAAATTATTTCCTATGACAATAAATTCCAAATATATGCTGAAGGGGATTGGCAACCTGCTGTCTATAATACAAAAAAACAGATACTAGAAAAAAGCTCTTCCACTCCACCACAAGTGACTGTGGCGACTCTATGCTCTTATTTTCAAAATTTTGTTAGAGTTTTGCTTACAGACTCCCAAGGGAATCTTTCTTCTTTTGAAGATCACAATCTTAACCTAGAAGAGTTCTTATCCCACCCCACATCTTCAGTACAAGATCACTCTCTGCATGTAATTTATGCTATTCTAGCAAACGATGAATCCTCTAAAAAGTTATCATCCTCCCAAGTAGCAAAAAATCCGGTATCCATAGAGTCTATTATTCTTCCTATAAAAGGATTTGGTTTATGGGGACCAATCTATGGATTTCTTGCTTTAGAAAAGGACGGTAATACGGTTCTAGGGACATGCTGGTATCAACATGGTGAGACTCCAGGATTAGGAGCAAATATAACTAATCCCCAATGGCAACAAAATTTCAGAGGAAAAAAAGTATTTCTCGCTTCCTCTTCCGGAGAAACCGATTTTGCTAAAACAACTCTAGGACTAGAAGTTATAAAAGGATCTGTTTCTGCATTATTAGGGGACTCTCCCAAAGCTAATTCCGCTGTTGATGGAATTTCAGGAGCTACACTGACCTGTAATGGAGTTACTGAAGCTTTTGCTAATTCGCTAGCTCCTTACCGCCCCTTATTGACTTTCTTCGCCAATCTTAACTCTAGTGGAGAATCTCATGACAACCAATAASEQ ID NO: 26: CM homologue of CT279 protein sequence = TC_0551protein sequenceMASKSRHYLNQPWYIILFIFVLSLVAGTLLSSVSYVLSPIQKQAAEFDRNQQMLMAAQIISYDNKFQIYAEGDWQPAVYNTKKQILEKSSSTPPQVTVATLCSYFQNFVRVLLTDSQGNLSSFEDHNLNLEEFLSHPTSSVQDHSLHVIYAILANDESSKKLSSSQVAKNPVSIESIILPIKGFGLWGPIYGFLALEKDGNTVLGTCWYQHGETPGLGANITNPQWQQNFRGKKVFLASSSGETDFAKTTLGLEVIKGSVSALLGDSPKANSAVDGISGATLTCNGVTEAFANSLAPYRPLLTFFANLNSSGESHDNQ SEQ ID NO: 27: CM homologue of CT372 =TC_0651 nucleotide sequenceATGAATGGAAAAGTTCTGTGTGAGGTTTCTGTGTCCTTCCGTTCGATTCTGCTGACGGCTCTGCTTTCACTTTCTTTTACAAACACTATGCAGGCTGCACACCATCATTATCACCGTTATGATGATAAACTACGCAGACAATACCATAAAAAGGACTTGCCCACTCAAGAGAATGTTCGGAAAGAGTTTTGTAATCCCTACTCTCATAGTAGTGATCCTATCCCTTTGTCACAACAACGAGGAGTCCTATCTCCTATCTGTGATTTAGTCTCAGAGTGCTCGTTTTTGAACGGGATTTCCGTTAGGAGTCTTAAACAAACACTGAAAAATTCTGCTGGGACTCAAGTTGCTTTAGACTGGTCTATCCTTCCTCAATGGTTCAATCCTAGATCCTCTTGGGCTCCTAAGCTCTCTATTCGAGATCTTGGATATGGTAAACCCCAGTCCCTTATTGAAGCAGATTCCCCTTGTTGTCAAACCTGCTTCAACCCATCTGCTGCTATTACGATTTACGATTCTTCATGTGGGAAGGGTGTTGTCCAAGTGTCATACACCCTTGTTCGTTATTGGAGAGAAACGGCTGCACTTGCAGGGCAAACTATGATGCTTGCAGGAAGTATTAATGATTATCCTGCTCGCCAAAACATATTCTCTCAACTTACATTTTCCCAAACTTTCCCTAATGAGAGAGTAAATCTAACTGTTGGTCAATACTCTCTTTACTCGATAGACGGAACGCTGTACAACAATGATCAGCAGCTAGGATTTATTAGTTATGCGTTGTCGCAAAATCCAACAGCGACTTATTCCTCTGGAAGCCTTGGCGCCTATCTACAAGTCGCTCCAACAGAAAGCACCTGTCTTCAAGTTGGGTTCCAAGATGCCTATAATATTTCAGGTTCCTCGATCAAATGGAATAATCTTACAAAAAATAAGTATAACTTCCATGGCTATGCATCTTGGGCTCCACACTGTTGCTTAGGACCTGGACAATACTCTGTTCTTCTTTATGTAACCAGAAAGGTTCCTGAGCAAATGATGCAGACAATGGGCTGGTCTGTGAATGCAAGTCAATACATCTCTTCTAAACTTTATGTATTTGGAAGATACAGCGGAGTCACAGGCCAATTGTCTCCTATTAACCGAACCTATTCATTTGGCTTAGTCTCTCCTAATTTATTGAACCGTAACCCACAAGACTTATTTGGAGTAGCTTGCGCATTCAATAATATACACGCCTCCGCCTTTCAAAATGCTCAAAGAAAATATGAAACTGTGATCGAGGGATTTGCAACTATTGGTTGCGGACCTTACATCTCCTTTGCTCCAGATTTCCAACTTTACCTCTATCCTGCTCTGCGTCCAAATAAACAAAGCGCCCGAGTCTATAGCGTTCGCGCAAACCTAGCTATTTAG SEQ ID NO: 28: CM homologue of CT372 =TC_0651 protein sequenceMNGKVLCEVSVSFRSILLTALLSLSFTNTMQAAHHHYHRYDDKLRRQYNKKDLPTQENVRKEFCNPYSHSSDPIPLSQQRGVLSPICDLVSECSFLNGISVRSLKQTLKNSAGTRVALDWSILPQWFNPRSSWAPKLSIRDLGYGKPQSLIEADSPCCQTCFNPSAAITIYDSSCGKGVVQVSYTLVRYWRETAALAGQTMMLAGSINDYPARQNIFSQLTFSQTFPNERVNLTVGQYSLYSIDGTLYNNDQQLGFISYALSQNPTATYSSGSLGAYLQVAPTESTCLQVGFRDAYNISGSSIKWNNLTKNKYNFHGYASWAPHCCLGPGQYSVLLYVTRKVPEQMMQTMGWSVNASQYISSKLYVFGRYSGVTGQLSPINRTYSFGLVSPNLLNRNPQDLFGVACAFNNIHASAFRNAQRKYETVIEGFATIGCGPYISFAPDFQLYLYPALRPNKRSARVYSVRANLAI SEQ ID NO: 29: CM homologue of CT443 = TC_0727ATGCGAATAGGAGATCCTATGAACAAACTCATCAGACGAGCTGTGACGATCTTCGCGGTGACTAGTGTGGCGAGTTTATTTGCTAGCGGGGTGTTAGAGACCTCTATGGCAGAGTCTCTCTCTACCAACGTTATTAGCTTAGCTGACACCAAAGCGAAAGAGACCACTTCTCATCAAAAAGACAGAAAAGCAAGAAAAAATCATCAAAATAGGACTTCCGTAGTCCGTAAAGAGGTTACTGCAGTTCGTGATACTAAAGCTGTAGAGCCTAGACAGGATTCTTGCTTTGGCAAAATGTATACAGTCAAAGTTAATGATGATCGTAATGTAGAAATCGTGCAGTCCGTTCCTGAATATGCTACGGTAGGATCTCCATATCCTATTGAGATTACTGCTATAGGGAAAAGAGACTGTGTTGATGTAATCATTACACAGCAATTACCATGCGAAGCAGAGTTTGTTAGCAGTGATCCAGCTACTACTCCTACTGCTGATGGTAAGCTAGTTTGGAAAATTGATCGGTTAGGACAGGGCGAAAAGAGTAAAATTACTGTATGGGTAAAACCTCTTAAAGAAGGTTGCTGCTTTACAGCTGCAACGGTTTGTGCTTGTCCAGAGATCCGTTCGGTTACGAAATGTGGCCAGCCTGCTATCTGTGTTAAACAGGAAGGTCCAGAAAGCGCATGTTTGCGTTGCCCAGTAACTTATAGAATTAATGTAGTCAACCAAGGAACAGCAACAGCACGTAATGTTGTTGTGGAAAATCCTGTTCCAGATGGCTATGCTCATGCATCCGGACAGCGTGTATTGACATATACTCTTGGGGATATGCAACCTGGAGAACAGAGAACAATCACCGTGGAGTTTTGTCCGCTTAAACGTGGTCGAGTCACAAATATTGCTACAGTTTCTTACTGTGGTGGACACAAAAATACTGCTAGCGTAACAACAGTGATCAATGAGCCTTGCGTGCAAGTTAACATCGAGGGAGCAGATTGGTCTTATGTTTGTAAGCCTGTAGAATATGTTATCTCTGTTTCTAACCCTGGTGACTTAGTTTTACGAGACGTTGTAATTGAAGATACGCTTTCTCCTGGAATAACTGTTGTTGAAGCAGCTGGAGCTCAGATTTCTTGTAATAAATTGGTTTGGACTTTGAAGGAACTCAATCCTGGAGAGTCTTTACAATATAAGGTTCTAGTAAGAGCTCAAACTCCAGGGCAATTCACAAACAACGTTGTTGTGAAAAGTTGCTCTGATTGCGGTATTTGTACTTCTTGCGCAGAAGCAACAACTTACTGGAAAGGAGTTGCTGCTACTCATATGTGCGTAGTAGATACTTGTGATCCTATTTGCGTAGGAGAGAACACTGTTTATCGTATCTGTGTGACAAACAGAGGTTCTGCTGAAGATACAAATGTGTCCTTAATTTTGAAATTCTCTAAAGAATTACAACCTATATCTTTCTCTGGACCAACTAAAGGAACCATTACAGGAAACACGGTAGTGTTTGATTCGTTACCTAGATTAGGTTCTAAAGAAACTGTAGAGTTTTCTGTAACGTTGAAAGCAGTATCCGCTGGAGATGCTCGTGGGGAAGCTATTCTTTCTTCCGATACATTGACAGTTCCTGTATCTGATACGGAGAATACACATATCTATTAASEQ ID NO: 30: CM homologue of CT443 = TC_0727MRIGDPMNKLIRRAVTIFAVTSVASLFASGVLETSMAESLSTNVISLADTKAKETTSHQKDRKARKNHQNRTSVVRKEVTAVRDTKAVEPRQDSCFGKMYTVKVNDDRNVEIVQSVPEYATVGSPYPIEITAIGKRDCVDVIITQQLPCEAEFVSSDPATTPTADGKLVWKIDRLGQGEKSKITVWVKPLKEGCCFTAATVCACPEIRSVTKCGQPAICVKQEGPESACLRCPVTYRINVVNQGTATARNVVVENPVPDGYAHASGQRVLTYTLGDMQPGEQRTITVEFCPLKRGRVTNIATVSYCGGHKNTASVTTVINEPCVQVNIEGADWSYVCKPVEYVISVSNPGDLVLRDVVIEDTLSPGITVVEAAGAQISCNKLVWTLKELNPGESLQYKVLVRAQTPGQFTNNVVVKSCSDCGICTSCAEATTYWKGVAATHMCVVDTCDPICVGENTVYRICVTNRGSAEDTNVSLILKFSKELQPISFSGPTKGTITGNTVVFDSLPRLGSKETVEFSVTLKAVSAGDARGEAILSSDTLTVPVSDTENTHIY SEQ ID NO: 31: CM homologue of CT043 =TC_0313 nucleotide sequenceATGTCCAGACAGAATGCTGAGGAAAATCTAAAAAATTTTGCTAAAGAGCTCAAGCTCCCCGACGTGGCCTTCGATCAGAATAATACGTGCATTTTGTTTGTTGATGGAGAGTTTTCTCTTCACCTGACCTACGAAGAGCACTCTGATCGCCTTTATGTTTACGCACCTCTCCTTGACGGACTCCCAGATAATCCGCAAAGAAAGTTGGCTCTGTATGAGAAATTGTTGGAAGGCTCTATGCTCGGAGGCCAAATGGCTGGTGGAGGAGTAGGAGTTGCTACTAAAGAACAGTTGATCCTAATGCATTGCGTGTTAGATATGAAATATGCAGAGACTAATCTATTGAAAGCTTTTGCACAGCTTTTCATTGAAACTGTTGTGAAATGGCGAACGGTCTGTTCTGATATCAGCGCTGGACGAGAACCTTCCGTTGACACTATGCCTCAAATGCCTCAAGGAGGCAGCGGAGGAATTCAACCTCCTCCAACAGGAATTCGTGCGTAGSEQ ID NO: 32: CM homologue of CT043 = TC_0313 protein sequenceMSRQNAEENLKNFAKELKLPDVAFDQNNTCILFVDGEFSLHLTYEEHSDRLYVYAPLLDGLPDNPQRKLALYEKLLEGSMLGGQMAGGGVGVATKEQLILMHCVLDMKYAETNLLKAFAQLFIETVVKWRTVCSDISAGREPSVDTMPQMPQGGSGGIQPPPTGIRA SEQ ID NO: 33: CM homologue of CT601 =TC_0890 nucleotide sequenceATGCTCGCTAATCGGTTATTTCTAATCACCCTTATAGGTTTTGGCTATTCTGCTTACGGTGCCAGCACAGGGAAATCACCTTCTTTACAGGTTATTTTAGCTGAAGTCGAGGATACATCTTCGCGCTTACAAGCTCATCAGAATGAGCTTGTTATGCTCTCGGAACGTTTAGATGAGCAAGACACAAAACTTCAACAACTCTCGTCAACTCAGGCCCGTAATCTTCCTCAACAAGTTCAACGGCTTGAGATTGATCTGAGAGCTCTGGCTAAAACAGCTGCTGTGCTCTCGCAATCTGTTCAGGATATCCGATCATCCGTGCAAAATAAATTACAAGAAATCCAACAAGAACAAAAAAATTTAGCTCAAAATTTACGAGCGCTTCGCAACTCCTTACAAGCACTAGTTGATGGCTCTTCCCCAGAAAATTATATTGATTTTTTGGCCGGGGAGACACCTGAACATATTCACGTTGTTAAACAAGGAGAAACCCTGAGTAAAATCGCTAGTAAGTACAATATCCCTGTCGCAGAATTGAAAAAACTTAATAAATTAAATTCCGATACTATTTTTACTGATCAAAGAATCCGACTTCCAAAAAAGAAATAASEQ ID NO: 34: CM homologue of CT601 = TC_0890 protein sequenceMLANRLFLITLIGFGYSAYGASTGKSPSLQVILAEVEDTSSRLQAHQNELVMLSERLDEQDTKLQQLSSTQARNLPQQVQRLEIDLRALAKTAAVLSQSVQDIRSSVQNKLQEIQQEQKNLAQNLRALRNSLQALVDGSSPENYIDFLAGETPEHIHVVKQGETLSKIASKYNIPVAELKKLNKLNSDTIFTDQRIRLPKKKSEQ ID NO: 35: CM homologue of CT456 = TC_0741ATGACGACTCCAATAAGTAATTCTCCATCTTCTATTCCAACTGTTACAGTATCAACTACTACAGCATCTTCTGGATCTCTCGGAACTTCTACTGTATCATCAACGACTACAAGTACTTCAGTCGCACAAACAGCAACAACAACATCTTCTGCTTCTACATCTATAATTCAGTCTAGTGGAGAAAACATCCAATCCACTACAGGTACCCCTTCTCCTATTACGTCTAGTGTTTCAACATCCGCTCCATCTCCTAAAGCCTCCGCCACTGCAAACAAAACTTCAAGCGCTGTTTCTGGGAAAATTACCTCACAAGAAACTTCTGAGGAATCCGAAACCCAAGCCACTACATCTGATGGAGAAGTTAGTAGTAATTACGATGATGTTGATACCCCGACCAATTCGTCCGATTCGACAGTTGATAGTGATTACCAAGATGTTGAGACTCAGTACAAAACAATTAGCAACAATGGTGAAAACACTTATGAAACAATCGGAAGTCATGGTGAGAAAAACACACACGTCCAGGAAAGCCATGCATCCGGAACAGGAAATCCCATAAATAATCAGCAAGAAGCTATTAGACAGCTCCGATCATCTACCTATACAACCAGCCCTCGTAATGAGAATATATTTAGTCCAGGACCGGAAGGTCTACCTAATATGTCTCTTCCTAGTTACAGCCCTACAGATAAAAGTTCTCTACTAGCTTTCCTATCTAATCCCAATACAAAAGCAAAAATGCTCGAACACTCCGGGCATTTAGTCTTTATAGACACAACTAGAAGTAGCTTTATCTTTGTTCCGAATGGAAATTGGGATCAAGTCTGTTCCATGAAGGTTCAGAATGGGAAAACTAAAGAAGACCTTGGCTTAAAGGACTTAGAAGATATGTGTGCAAAGTTTTGCACAGGATACAATAAATTCTCCTCTGATTGGGGAAATCGAGTTGACCCCTTGGTCTCTTCTAAGGCCGGGATAGAAAGTGGGGGGCACCTCCCAAGCTCAGTTATCATCAACAACAAATTTAGAACCTGTGTTGCCTATGGGCCGTGGAACCCCAAAGAAAACGGCCCCAATTATACTCCTTCAGCCTGGAGACGTGGGCATCGAGTAGATTTTGGAAAGATCTTTGATGGAACAGCGCCGTTTAATAAAATCAACTGGGGCTCTTCCCCTACCCCTGGTGATGACGGCATCTCCTTCTCTAATGAAACTATTGGGTCTGAACCATTCGCGACACCTCCCTCATCCCCATCGCAAACCCCCGTTATCAACGTCAATGTTAATGTCGGTGGAACCAATGTTAATATTGGGGATACAAACGTATCTAAAGGATCCGGCACACCAACATCTTCTCAATCTGTGGACATGTCTACAGATACTAGCGATTTAGATACCAGTGATATTGATACAAACAACCAAACTAACGGCGATATCAACACGAATGACAACTCCAATAATGTCGATGGAAGTTTATCTGACGTTGATTCAAGGGTGGAAGACGATGACGGTGTATCGGATACAGAGTCCACTAATGGCAATGACTCTGGTAAAACTACTTCCACAGAAGAAAATGGTGACCCAAGCGGACCAGACATCCTGGCTGCTGTACGTAAACACCTAGACACTGTCTATCCAGGAGAAAATGGCGGATCTACAGAAGGACCTCTCCCTGCTAATCAAAATCTGGGGAACGTTATCCATGATGTGGAGCAGAATGGATCTGCTAAAGAAACTATTATCACTCCAGGAGATACAGGGCCTACAGACTCAAGCTCCTCTGTAGATGCTGATGCAGACGTTGAAGATACTTCTGATACTGACTCTGGAATCGGAGACGACGACGGTGTATCGGATACAGAGTCCACTAATGGTAATAACTCTGGTAAAACTACTTCCACAGAAGAAAATGGTGACCCAAGCGGACCAGACATCCTGGCTGCTGTACGTAAACACCTAGACACTGTCTATCCAGGAGAAAATGGCGGATCTACAGAAGGACCTCTCCCTGCTAATCAAAATCTGGGGAACGTTATCCATGATGTAGAACAAAACGGAGCCGCTCAAGAAACTATTATCACTCCAGGAGATACGGAATCTACAGACACAAGCTCTAGTGTAAATGCTAATGCAGACTTAGAAGATGTTTCTGATGCTGATTCAGGATTCGGGGATGATGACGGTATATCGGATACAGAGTCCACTAATGGTAACGACTCTGGAAAAAATACTCCTGTAGGGGATGGTGGTACACCAAGCGGACCAGATATCCTAGCTGCTGTACGCAAACATCTAGACACTGTCTATCCAGGAGAAAATGGTGGATCTACAGAGAGACCTTTACCCGCTAATCAAAATTTAGGAGATATCATTCATGATGTAGAACAAAACGGAAGCGCTAAAGAAACTGTAGTATCGCCTTATCGAGGAGGAGGAGGAAATACATCTTCCCCAATTGGATTAGCCTCCCTGCTTCCAGCAACACCATCCACACCTTTGATGACAACACCTAGAACAAATGGGAAAGCTGCAGCTTCTTCTTTGATGATAAAAGGAGGAGAAACTCAAGCCAAGCTAGTTAAGAATGGCGGCAATATCCCTGGAGAAACCACATTAGCAGAATTACTCCCTCGTTTAAGAGGACACCTTGACAAAGTCTTTACTTCAGACGGGAAGTTTACAAATCTTAATGGACCTCAACTTGGAGCCATCATAGACCAATTCCGCAAAGAAACGGGTTCCGGAGGAATCATAGCTCATACAGATAGTGTTCCAGGAGAGAACGGAACAGCCTCTCCTCTCACAGGAAGTTCAGGGGAAAAAGTCTCTCTCTATGATGCAGCGAAAAACGTCACTCAAGCTTTAACAAGTGTTACGAACAAAGTAACCCTAGCAATGCAAGGACAAAAACTGGAAGGAATTATAAACAACAACAATACCCCCTCTTCTATTGGACAAAATCTTTTCGCAGCAGCGAGGGCAACGACACAATCCCTCAGTTCATTAATTGGAACCGTACAATAA SEQ ID NO: 36: CM homologue of CT456 =TC_0741 protein sequenceMTTPISNSPSSIPTVTVSTTTASSGSLGTSTVSSTTTSTSVAQTATTTSSASTSIIQSSGENIQSTTGTPSPITSSVSTSAPSPKASATANKTSSAVSGKITSQETSEESETQATTSDGEVSSNYDDVDTPTNSSDSTVDSDYQDVETQYKTISNNGENTYETIGSHGEKNTHVQESHASGTGNPINNQQEAIRQLRSSTYTTSPRNENIFSPGPEGLPNMSLPSYSPTDKSSLLAFLSNPNTKAKMLEHSGHLVFIDTTRSSFIFVPNGNWDQVCSMKVQNGKTKEDLGLKDLEDMCAKFCTGYNKFSSDWGNRVDPLVSSKAGIESGGHLPSSVIINNKFRICVAYGPWNPKENGPNYTPSAWRRGHRVDFGKIFDGTAPFNKINWGSSPTPGDDGISFSNETIGSEPFATPPSSPSQTPVINVNVNVGGTNVNIGDTNVSKGSGTPTSSQSVDMSTDTSDLDTSDIDTNNQTNGDINTNDNSNNVDGSLSDVDSRVEDDDGVSDTESTNGNDSGKTTSTEENGDPSGPDILAAVRKHLDTVYPGENGGSTEGPLPANQNLGNVIHDVEQNGSAKETIITPGDTGPTDSSSSVDADADVEDTSDTDSGIGDDDGVSDTESTNGNNSGKTTSTEENGDPSGPDILAAVRKHLDTVYPGENGGSTEGPLPANQNLGNVIHDVEQNGAAQETIITPGDTESTDTSSSVNANADLEDVSDADSGFGDDDGISDTESTNGNDSGKNTPVGDGGTPSGPDILAAVRKHLDTVYPGENGGSTERPLPANQNLGDIIHDVEQNGSAKETVVSPYRGGGGNTSSPIGLASLLPATPSTPLMTTPRTNGKAAASSLMIKGGETQAKLVKNGGNIPGETTLAELLPRLRGHLDKVFTSDGKFTNLNGPQLGAIIDQFRKETGSGGIIAHTDSVPGENGTASPLTGSSGEKVSLYDAAKNVTQALTSVTNKVTLAMQGQKLEGIINNNNTPSSIGQNLFAAARATTQSLSSLIGTVQ SEQ ID NO: 37: CM homologue of CT381 = TC_0660GTGAGTATGTATATAAAAAGAAAGAAAGCTTGGATGACTTTCTTAGCAATTGTCTGTAGTTTCTGTTTGGCGGGCTGTTCAAAAGAGAGCAAAGACTCTGTTAGTGAAAAATTTATTGTAGGAACTAACGCAACGTATCCTCCTTTTGAGTTTGTTGATGAAAGAGGTGAGACGGTTGGCTTTGATATTGATTTAGCTAGGGAGATTAGTAAAAAGCTAGGGAAAAAATTAGAAGTCCGAGAATTTGCTTTTGATGCACTCGTTCTCAATTTAAAACAGCATCGTATTGATGCAATTATGGCAGGGGTGTCCATTACGTCTTCTCGATTGAAAGAAATTTTGATGATTCCCTACTATGGCGAAGAAATAAAGAGTTTGGTTTTAGTGTTTAAGGATGGAGACTCAAAGTCTTTACCACTAGATCAGTATAATTCTGTTGCTGTTCAAACTGGCACGTACCAAGAGGAATATTTACAGTCTCTTCCAGGGGTGCGTATTCGCTCTTTTGATAGTACTTTAGAAGTGCTTATGGAAGTTTTGCATAGCAAGTCTCCTATAGCTGTTTTAGAACCGTCTATTGCGCAGGTCGTTTTAAAAGATTTTCCGACGCTCACTACTGAAACGATAGATCTTCCTGAAGATAAATGGGTTTTAGGGTATCGAATTGGAGTTGCTTCTGATCGACCATCTCTAGCTTCTGATATAGAAGCTGCTGTACAAGAGATCAAGAAAGAAGGAGTGTTAGCAGAGTTAGAGCAAAAATGGGGTTTGAACGGCTAA SEQ ID NO: 38: CM homologue of CT381 = TC_0660MSMYIKRKKAWMTFLAIVCSFCLAGCSKESKDSVSEKFIVGTNATYPPFEFVDERGETVGFDIDLAREISKKLGKKLEVREFAFDALVLNLKQHRIDAIMAGVSITSSRLKEILMIPYYGEEIKSLVLVFKDGDSKSLPLDQYNSVAVQTGTYQEEYLQSLPGVRIRSFDSTLEVLMEVLHSKSPIAVLEPSIAQVVLKDFPTLTTETIDLPEDKWVLGYGIGVASDRPSLASDIEAAVQEIKKEGVLAELEQKWGLNG SEQ ID NO: 39 - CT255 nucleotide sequenceATGGAAGAAAAAGGCATCTTACAATTGGTTGAAATTTCGCGAGCAATGGCTTTACAGGGAGTTTGTCCTTGGACTAATTTACAGAGTGTGGAGTCTATGTTGCAGTATATAGCAGGGGAGTGTCAGGAGTTGGCTGATGCTGTACAAGAAAATAAAGCTTCGTTGGAAATCGCTTCGGAAGCCGGAGACGTACTTACTTTAGTATTGACCTTGTGTTTCTTGCTAGAAAGAGAAGGAAAGCTTAAAGCTGAAGAAGTATTTGTAGAAGCTTTGGCTAAGTTGCGTCGTCGATCTCCTCATGTTTTTGATCCTCATAATCAAATTTCTTTAGAACAGGCTGAAGAATACTGGGCTCGTATGAAACAGCAAGAAAAAATTTCTTAASEQ ID NO: 40 - CT255 protein sequenceMEEKGILQLVEISRAMALQGVCPWTNLQSVESMLQYIAGECQELADAVQENKASLEIASEAGDVLTLVLTLCFLLEREGKLKAEEVFVEALAKLRRRSPHVFDPHNQISLEQAEEYWARMKQQEKISSEQ ID NO: 41 - CT341 nucleotide sequenceATGGATTACTACACGATATTGGGTGTAGCGAAGACTGCTACTCCTGAAGAAATAAAGAAAGCTTACCGTAAGCTCGCTGTAAAGTACCATCCAGATAAGAATCCTGGGGATGCTGAAGCGGAGCGACGCTTTAAAGAAGTTTCTGAAGCCTATGAAGTATTAGGTGATGCGCAGAAGCGGGAGTCATATGATCGTTACGGCAAAGACGGTCCATTTGCTGGTGCTGGAGGATTCGGTGGCGCTGGCATGGGGAATATGGAAGACGCTTTGCGAACATTTATGGGAGCTTTTGGCGGCGATTTCGGTGGTAATGGAGGCGGTTTCTTTGAAGGGCTTTTTGGAGGACTTGGAGAAGCTTTCGGAATGCGTGGAGGCTCAGAAAGTTCTCGACAAGGAGCTAGTAAGAAGGTGCATATTACGCTGTCCTTCGAGGAGGCGGCAAAAGGTGTTGAAAAAGAACTTCTTGTTTCAGGCTATAAATCTTGTGATGCTTGTTCTGGTAGTGGAGCCAATACTGCTAAAGGTGTAAAAGTTTGTGATCGATGCAAGGGCTCTGGTCAGGTAGTGCAAAGCCGAGGCTTTTTCTCCATGGCTTCTACTTGCCCTGATTGTAGTGGTGAAGGTCGGGTTATCACAGATCCTTGTTCAGTTTGTCGTGGGCAGGGACGTATCAAGGATAAACGTAGCGTCCATGTTAATATCCCAGCTGGAGTCGATTCTGGGATGAGATTAAAGATGGAAGGCTATGGAGATGCTGGCCAAAATGGAGCGCCTGCAGGGGATCTGTATGTTTTTATTGATGTAGAGCCTCATCCTGTTTTCGAGCGCCATGGGGATGATTTAGTTTTAGAGCTTCCTATTGGATTTGTTGATGCGGCTTTAGGGATCAAGAAGGAAATCCCTACACTCTTAAAAGAAGGTACTTGCCGTTTGAGTATCCCAGAAGGGATTCAGAGCGGAACAGTTCTTAAAGTTAGAGGGCAGGGATTCCCTAATGTGCATGGGAAATCCAGAGGAGATCTTTTAGTAAGAGTATCTGTGGAGACTCCCCAGCACCTATCTAATGAACAAAAAGATTTATTGAGACAGTTTGCTGCTACGGAGAAGGCTGAAAATTTCCCTAAGAAACGGAGTTTCTTAGACAAAATCAAAGGTTTTTTTTCTGACTTTGCTGTATAG SEQ ID NO: 42 - CT341 protein sequenceMDYYTILGVAKTATPEEIKKAYRKLAVKYHPDKNPGDAEAERRFKEVSEAYEVLGDAQKRESYDRYGKDGPFAGAGGFGGAGMGNMEDALRTFMGAFGGDFGGNGGGFFEGLFGGLGEAFGMRGGSESSRQGASKKVHITLSFEEAAKGVEKELLVSGYKSCDACSGSGANTAKGVKVCDRCKGSGQVVQSRGFFSMASTCPDCSGEGRVITDPCSVCRGQGRIKDKRSVHVNIPAGVDSGMRLKMEGYGDAGQNGAPAGDLYVFIDVEPHPVFERHGDDLVLELPIGFVDAALGIKKEIPTLLKEGTCRLSIPEGIQSGTVLKVRGQGFPNVHGKSRGDLLVRVSVETPQHLSNEQKDLLRQFAATEKAENFPKKRSFLDKIKGFFSDFAV SEQ ID NO: 43 - CT716 nucleotide sequenceATGAATAAAAAACTCCAAGATCTGTCTAAACTGCTCACTATTGAGCTTTTCAAGAAACGTACACGGTTGGAAACAGTAAAAAAAGCGCTCTCCACAATAGAACATCGCTTACAACAAATACAGGAGCACATCGCGAAAATTTCCTTAACAAGGCACAAACAATTCCTATGTCGGTCATATACCCATGAATATGACCAACATTTAGAACATTTACAAAGAGAGCAAACTTCTCTATATAAACAGCATCAGACCCTGAAAACGTCTTTGAAAGATGCTTATGGCGACATACAAAAACAACTAGACCAAAGAAAAATTATCGAAAAGATCCATGACAGTAAATATCCTATAAAGAGCGCGAATAACTAASEQ ID NO: 44 - CT716 protein sequenceMNKKLQDLSKLLTIELFKKRTRLETVKKALSTIEHRLQQIQEHIAKISLTRHKQFLCRSYTHEYDQHLEHLQREQTSLYKQHQTLKTSLKDAYGDIQKQLDQRKIIEKIHDSKYPIKSANNSEQ ID NO: 45 - CT745 nucleotide sequenceATGAAACATGCTCTCATTGTTGGCTCAGGTATTGCCGGCCTTTCTGCCGCGTGGTGGCTACACAAACGATTCCCTCATGTGCAGCTGTCTATTCTAGAAAAAGAGTCTCGATCTGGAGGGCTAATTGTCACAGAGAAACAACAAGGGTTTTCCCTCAATATGGGCCCTAAAGGTTTTGTTTTAGCTCATGATGGGCAACACACCCTTCACCTCATTCAGTCTTTAGGCCTAGCAGACGAGCTATTATATAGCTCTCCAGAGGCTAAAAACCGCTTTATCCACTATAATAATAAAACCCGAAAAGTCTCGCCTTGGACTATTTTCAAACAAAATCTCCCTCTCTCTTTTGCTAAGGATTTCTTTGCGCGTCCTTACAAACAAGACAGCTCCGTGGAAGCCTTCTTTAAAAGACACAGTTCTTCCAAGCTTAGAAGAAATCTTTTAAATCCCATTAGCATTGCTATTCGTGCAGGACATAGTCATATATTGTCTGCACAGATGGCTTACCCAGAATTAACACGAAGAGAAGCTCAAACAGGATCGTTGTTACGTAGTTATCTCAAAGATTTTCCTAAAGAGAAACGCACAGGCCCTTATTTAGCTACCTTGCGGTCTGGGATGGGAATGCTAACCCAGGCTTTGCATGATAAATTGCCTGCTACCTGGTATTTTTCTGCACCCGTCAGCAAAATCCGTCAGTTGGCGAATGGGAAAATTTCTCTTTCATCTCCTCAAGGAGAAATAACGGGAGATATGCTCATTTATGCTGGGTCCGTGCACGATCTCCCTTCCTGTCTAGAAGGGATCCCTGAAACCAAGCTTATCAAGCAAACGACTTCATCTTGGGATCTCTCTTGTGTATCTTTAGGATGGCATGCATCCTTCCCTATCCCTCATGGATATGGCATGCTTTTCGCTGATACGCCTCCCTTATTAGGGATCGTGTTTAATACGGAAGTGTTCCCTCAACCCGAGCGGCCTAATACAATAGTCTCTCTTCTTTTAGAAGGTCGATGGCACCAAGAAGAAGCGTATGCTTTCTCACTAGCAGCTATTTCTGAGTACCTGCAAATTTACACTCCTCCCCAAGCTTTCTCACTATTCTCTCCTCGAGAGGGACTTCCCCAACACCATGTTGGATTTATCCAATCCCGCCAACGCCTTCTATCTAAACTTCCTCACAATATAAAAATTGTAGGGCAGAATTTTGCAGGTCCAGGTCTCAACCGCGCTACAGCGTCTGCTTATAAAGCTATAGCTTCTTTACTATCATGASEQ ID NO: 46 - CT745 protein sequenceMKHALIVGSGIAGLSAAWWLHKRFPHVQLSILEKESRSGGLIVTEKQQGFSLNMGPKGFVLAHDGQHTLHLIQSLGLADELLYSSPEAKNRFIHYNNKTRKVSPWTIFKQNLPLSFAKDFFARPYKQDSSVEAFFKRHSSSKLRRNLLNPISIAIRAGHSHILSAQMAYPELTRREAQTGSLLRSYLKDFPKEKRTGPYLATLRSGMGMLTQALHDKLPATWYFSAPVSKIRQLANGKISLSSPQGEITGDMLIYAGSVHDLPSCLEGIPETKLIKQTTSSWDLSCVSLGWHASFPIPHGYGMLFADTPPLLGIVFNTEVFPQPERPNTIVSLLLEGRWHQEEAYAFSLAAISEYLQIYIPPQAFSLFSPREGLPQHHVGFIQSRQRLLSKLPHNIKIVGQNFAGPGLNRATASAYKAIASLLSSEQ ID NO: 47 - CT387 nucleotide sequenceATGACGCTCTTTCATTCTCATCATGATGCCGTCTCTCCAGACAGCTACCTATGTTCTTCCCTTCAGTTAGTTGGTACTGGCGTATACGAAGGAGAAATCGAGATTCAAAATATCCCCTCTTATTTCCTTGGATTCCAATTACCCTCTCATTGCATACACCTTAATTTAAAGAGCTCTCTAGCTCAATTAGGAATAGATGCCTCCCTTCTTCACTGCGAATTGAGCAAAAATCAACATCGAGCACATATACATGCTCAATTTACCGGTCATGGCCCCATTGCTGAATCTATGCTAGCCCTTCTCCAACCAGGAGATCGTGTAGCAAAACTATTTGCTGCAGACGATCGCAGACTGGTCCGATCTCCAGATTACCTCGAAAGCATGCTGAAAAATACAGATAAAGCTGGCCATCCTTTGCTCTGTTTTGGGAAAAAATTAGAACACTTGATTTCTTTTGATGTGGTAGATGATCGCCTTGTCGTCTCCCTTCCTACCCTGCCGGGAGTTGTTCGTTATGATTCGGATATTTATGGACTCCTTCCTCTTATTCAAAAATCACTCAGTAATCCCAAACTCAGCATTCGTCACTTTTTAGCTCTGTACCAACAGATTGTGGAAGGGCAACATGTCTCTTGCGGAAACCATATTCTTCTGATCAAAACAGAACCGCTGCACATCCGCACTGTATTTGCTCGCGTGGTAAATCAACTCCTCCCTCAAGGTCTCTCCCACACTTCTGCCAATATTTTGGAACCAACCACTCGAGAATCCGGGGATATCTTTGAATTTTTTGGGAACCCTTCTGCACAGATAGAAAGAATTCCTTTAGAATTTTTCACTATCGAACCCTATAAAGAACATTCTTACTTCTGTAATCGGGATTTATTACAAACCATCTTACAATCAGAAAGCGAAATCAAAAAAATATTCGAAACAGCGCCCAAAGAACCTGTCAAAGCTGCCACCTATTTATCAAAAGGCAGTGAAATCTCTTCCCTGCACACAGACTCTTGGCTCACAGGATCCGCAGCTGCCTATCAATATAGTGAGCAAGCAGATAAAAACGAGTACACTCATGCTCAACCTTGCTATCCTTTCTTAGAAGCAATGGAAATGGGCCTGATCAATAGCGAAGGAGCCTTACTCACTCGTTATTTCCCTTCAGCTAGCTTAAAAGGAATGTTGATTTCCTACCATGTGCGCCACTATCTCAAACAAATCTACTTTCAAGTTCCCTCTTATACACATGGAAACTATTTCTCTCATAATGACAGAGGTTTGCTATTAGATCTGCAGCAAGCAGATATTGATGTTTTCTGGGCAGATGAAGAAAGCGGCCGTGTGTTGCAATATACAAAACGACGCGATAAGAATAGCGGTATGTTCGTGATCAAAAATCGTGTTGAAGAGTTTCGATCAGCTTATTTTATTGCTATTTATGGCTCTCGTCTCCTTGAGAATAATTTCTCTGCTCAGCTCCATACCCTCCTAGCGGGCTTACAGCAAGCAGCACATACTCTCGGCATTCCTGGATTCTCAAAGCCTACCCCACTTGCAGTCATCACCGGAGGCGGCACTGGAGTTATGGCCACAGGAAATCGTGTAGCTAAAGAACTAGGAATCCTATCTTGTGGAACCGTTCTTGATTTAGAAGCTTCTCCAGCACAAATCGACCAACCTACCAATGAATTCTTAGATGCTAAAATGACATACCGCCTACCTCAACTTATAGAAAGGCAAGAACACTTTTATGCAGACCTTCCTATCCTTGTAGTTGGCGGTGTAGGAACCGATTTCGAACTCTACCTAGAACTTGTCTATCTCAAAACAGGAGCTAAACCACCGACTCCCATTTTCCTAATTGGACCTATTGAATACTGGAAAGAAAAAGTGGCCCACGCCTACGAGATCAACCTCAAAGCAGGAACCATCCGTGGATCCGAATGGATCAGCAACTGCCTATATTGTATCACTTCTCCGGAAGCTGGAATTGCCGTATTCGAACAATTCCTAGCTGGAGAACTCCCTATAGGATACGACTATCCTCCAGCTCCAGATGGATTAGTGATCGTCTAASEQ ID NO: 48 - CT387 protein sequenceMTLFHSHHDAVSPDSYLCSSLQLVGTGVYEGEIEIQNIPSYFLGFQLPSHCIHLNLKSSLAQLGIDASLLHCELSKNQHRAHIHAQFTGHGPIAESMLALLQPGDRVAKLFAADDRRLVRSPDYLESMLKNTDKAGHPLLCFGKKLEHLISFDVVDDRLVVSLPTLPGVVRYDSDIYGLLPLIQKSLSNPKLSIRHFLALYQQIVEGQHVSCGNHILLIKTEPLHIRTVFARVVNQLLPQGLSHTSANILEPTTRESGDIFEFFGNPSAQIERIPLEFFTIEPYKEHSYFCNRDLLQTILQSESEIKKIFETAPKEPVKAATYLSKGSEISSLHTDSWLTGSAAAYQYSEQADKNEYTHAQPCYPFLEAMEMGLINSEGALLTRYFPSASLKGMLISYHVRHYLKQIYFQVPSYTHGNYFSHNDRGLLLDLQQADIDVFWADEESGRVLQYTKRRDKNSGMFVIKNRVEEFRSAYFIAIYGSRLLENNFSAQLHTLLAGLQQAAHTLGIPGFSKPTPLAVITGGGTGVMATGNRVAKELGILSCGTVLDLEASPAQIDQPTNEFLDAKMTYRLPQLIERQEHFYADLPILVVGGVGTDFELYLELVYLKTGAKPPTPIFLIGPIEYWKEKVAHAYEINLKAGTIRGSEWISNCLYCITSPEAGIAVFEQFLAGELPIGYDYPPAPDGLVIVSEQ ID NO: 49 - CT812 nucleotide sequenceATGAGTTCCGAGAAAGATATAAAAAGCACCTGTTCTAAGTTTTCTTTGTCTGTAGTAGCAGCTATCCTTGCCTCTGTTAGCGGGTTAGCTAGTTGCGTAGATCTTCATGCTGGAGGACAGTCTGTAAATGAGCTGGTATATGTAGGCCCTCAAGCGGTTTTATTGTTAGACCAAATTCGAGATCTATTCGTTGGGTCTAAAGATAGTCAGGCTGAAGGACAGTATAGGTTAATTGTAGGAGATCCAAGTTCTTTCCAAGAGAAAGATGCGGATACTCTTCCCGGGAAGGTAGAGCAAAGTACTTTGTTCTCAGTAACCAATCCCGTGGTTTTCCAAGGTGTGGACCAACAGGATCAAGTCTCTTCCCAAGGGTTAATTTGTAGTTTTACGAGCAGCAACCTTGATTCTCCTCGTGACGGAGAATCTTTTTTAGGTATTGCTTTTGTTGGGGATAGTAGTAAGGCTGGAATCACATTAACTGACGTGAAAGCTTCTTTGTCTGGAGCGGCTTTATATTCTACAGAAGATCTTATCTTTGAAAAGATTAAGGGTGGATTGGAATTTGCATCATGTTCTTCTCTAGAACAGGGGGGAGCTTGTGCAGCTCAAAGTATTTTGATTCATGATTGTCAAGGATTGCAGGTTAAACACTGTACTACAGCCGTGAATGCTGAGGGGTCTAGTGCGAATGATCATCTTGGATTTGGAGGAGGCGCTTTCTTTGTTACGGGTTCTCTTTCTGGAGAGAAAAGTCTCTATATGCCTGCAGGAGATATGGTAGTTGCGAATTGTGATGGGGCTATATCTTTTGAAGGAAACAGCGCGAACTTTGCTAATGGAGGAGCGATTGCTGCCTCTGGGAAAGTGCTTTTTGTCGCTAATGATAAAAAGACTTCTTTTATAGAGAACCGAGCTTTGTCTGGAGGAGCGATTGCAGCCTCTTCTGATATTGCCTTTCAAAACTGCGCAGAACTAGTTTTCAAAGGCAATTGTGCAATTGGAACAGAGGATAAAGGTTCTTTAGGTGGAGGGGCTATATCTTCTCTAGGCACCGTTCTTTTGCAAGGGAATCACGGGATAACTTGTGATAAGAATGAGTCTGCTTCGCAAGGAGGCGCCATTTTTGGCAAAAATTGTCAGATTTCTGACAACGAGGGGCCAGTGGTTTTCAGAGATAGTACAGCTTGCTTAGGAGGAGGCGCTATTGCAGCTCAAGAAATTGTTTCTATTCAGAACAATCAGGCTGGGATTTCCTTCGAGGGAGGTAAGGCTAGTTTCGGAGGAGGTATTGCGTGTGGATCTTTTTCTTCCGCAGGTGGTGCTTCTGTTTTAGGGACCATTGATATTTCGAAGAATTTAGGCGCGATTTCGTTCTCTCGTACTTTATGTACGACCTCAGATTTAGGACAAATGGAGTACCAGGGAGGAGGAGCTCTATTTGGTGAAAATATTTCTCTTTCTGAGAATGCTGGTGTGCTCACCTTTAAAGACAACATTGTGAAGACTTTTGCTTCGAATGGGAAAATTCTGGGAGGAGGAGCGATTTTAGCTACTGGTAAGGTGGAAATTACTAATAATTCCGAAGGAATTTCTTTTACAGGAAATGCGAGAGCTCCACAAGCTCTTCCAACTCAAGAGGAGTTTCCTTTATTCAGCAAAAAAGAAGGGCGACCACTCTCTTCAGGATATTCTGGGGGAGGAGCGATTTTAGGAAGAGAAGTAGCTATTCTCCACAACGCTGCAGTAGTATTTGAGCAAAATCGTTTGCAGTGCAGCGAAGAAGAAGCGACATTATTAGGTTGTTGTGGAGGAGGCGCTGTTCATGGGATGGATAGCACTTCGATTGTTGGCAACTCTTCAGTAAGATTTGGTAATAATTACGCAATGGGACAAGGAGTCTCAGGAGGAGCTCTTTTATCTAAAACAGTGCAGTTAGCTGGGAATGGAAGCGTCGATTTTTCTCGAAATATTGCTAGTTTGGGAGGAGGAGCTCTTCAAGCTTCTGAAGGAAATTGTGAGCTAGTTGATAACGGCTATGTGCTATTCAGAGATAATCGAGGGAGGGTTTATGGGGGTGCTATTTCTTGCTTACGTGGAGATGTAGTCATTTCTGGAAACAAGGGTAGAGTTGAATTTAAAGACAACATAGCAACACGTCTTTATGTGGAAGAAACTGTAGAAAAGGTTGAAGAGGTAGAGCCAGCTCCTGAGCAAAAAGACAATAATGAGCTTTCTTTCTTAGGGAGAGCAGAACAGAGTTTTATTACTGCAGCTAATCAAGCTCTTTTCGCATCTGAAGATGGGGATTTATCACCTGAGTCATCCATTTCTTCTGAAGAACTTGCGAAAAGAAGAGAGTGTGCTGGAGGAGCTATTTTTGCAAAACGGGTTCGTATTGTAGATAACCAAGAGGCCGTTGTATTCTCGAATAACTTCTCTGATATTTATGGCGGCGCCATTTTTACAGGTTCTCTTCGAGAAGAGGATAAGTTAGATGGGCAAATCCCTGAAGTCTTGATCTCAGGCAATGCAGGGGATGTTGTTTTTTCCGGAAATTCCTCGAAGCGTGATGAGCATCTTCCTCATACAGGTGGGGGAGCCATTTGTACTCAAAATTTGACGATTTCTCAGAATACAGGGAATGTTCTGTTTTATAACAACGTGGCCTGTTCGGGAGGAGCTGTTCGTATAGAGGATCATGGTAATGTTCTTTTAGAAGCTTTTGGAGGAGATATTGTTTTTAAAGGAAATTCTTCTTTCAGAGCACAAGGATCCGATGCTATCTATTTTGCAGGTAAAGAATCGCATATTACAGCCCTGAATGCTACGGAAGGACATGCTATTGTTTTCCACGACGCATTAGTTTTTGAAAATCTAGAAGAAAGGAAATCTGCTGAAGTATTGTTAATCAATAGTCGAGAAAATCCAGGTTACACTGGATCTATTCGATTTTTAGAAGCAGAAAGTAAAGTTCCTCAATGTATTCATGTACAACAAGGAAGCCTTGAGTTGCTAAATGGAGCCACATTATGTAGTTATGGTTTTAAACAAGATGCTGGAGCTAAGTTGGTATTGGCTGCTGGAGCTAAACTGAAGATTTTAGATTCAGGAACTCCTGTACAACAAGGGCATGCTATCAGTAAACCTGAAGCAGAAATCGAGTCATCTTCTGAACCAGAGGGTGCACATTCTCTTTGGATTGCGAAGAATGCTCAAACAACAGTTCCTATGGTTGATATCCATACTATTTCTGTAGATTTAGCCTCCTTCTCTTCTAGTCAACAGGAGGGGACAGTAGAAGCTCCTCAGGTTATTGTTCCTGGAGGAAGTTATGTTCGATCTGGAGAGCTTAATTTGGAGTTAGTTAACACAACAGGTACTGGTTATGAAAATCATGCTTTATTGAAGAATGAGGCTAAAGTTCCATTGATGTCTTTCGTTGCTTCTGGTGATGAAGCTTCAGCCGAAATCAGTAACTTGTCGGTTTCTGATTTACAGATTCATGTAGTAACTCCAGAGATTGAAGAAGACACATACGGCCATATGGGAGATTGGTCTGAGGCTAAAATTCAAGATGGAACTCTTGTCATTAGTTGGAATCCTACTGGATATCGATTAGATCCTCAAAAAGCAGGGGCTTTAGTATTTAATGCATTATGGGAAGAAGGGGCTGTCTTGTCTGCTCTGAAAAATGCACGCTTTGCTCATAATCTCACTGCTCAGCGTATGGAATTCGATTATTCTACAAATGTGTGGGGATTCGCCTTTGGTGGTTTCCGAACTCTATCTGCAGAGAATCTGGTTGCTATTGATGGATACAAAGGAGCTTATGGTGGTGCTTCTGCTGGAGTCGATATTCAATTGATGGAAGATTTTGTTCTAGGAGTTAGTGGAGCTGCTTTCCTAGGTAAAATGGATAGTCAGAAGTTTGATGCGGAGGTTTCTCGGAAGGGAGTTGTTGGTTCTGTATATACAGGATTTTTAGCTGGATCCTGGTTCTTCAAAGGACAATATAGCCTTGGAGAAACACAGAACGATATGAAAACGCGTTATGGAGTACTAGGAGAGTCGAGTGCTTCTTGGACATCTCGAGGAGTACTGGCAGATGCTTTAGTTGAATACCGAAGTTTAGTTGGTCCTGTGAGACCTACTTTTTATGCTTTGCATTTCAATCCTTATGTCGAAGTATCTTATGCTTCTATGAAATTCCCTGGCTTTACAGAACAAGGAAGAGAAGCGCGTTCTTTTGAAGACGCTTCCCTTACCAATATCACCATTCCTTTAGGGATGAAGTTTGAATTGGCGTTCATAAAAGGACAGTTTTCAGAGGTGAACTCTTTGGGAATAAGTTATGCATGGGAAGCTTATCGAAAAGTAGAAGGAGGCGCGGTGCAGCTTTTAGAAGCTGGGTTTGATTGGGAGGGAGCTCCAATGGATCTTCCTAGACAGGAGCTGCGTGTCGCTCTGGAAAATAATACGGAATGGAGTTCTTACTTCAGCACAGTCTTAGGATTAACAGCTTTTTGTGGAGGATTTACTTCTACAGATAGTAAACTAGGATATGAGGCGAATACTGGATTGCGATTGATCTTTTAASEQ ID NO: 50 - CT812 protein sequenceMSSEKDIKSTCSKFSLSVVAAILASVSGLASCVDLHAGGQSVNELVYVGPQAVLLLDQIRDLFVGSKDSQAEGQYRLIVGDPSSFQEKDADTLPGKVEQSTLFSVTNPVVFQGVDQQDQVSSQGLICSFTSSNLDSPRDGESFLGIAFVGDSSKAGITLTDVKASLSGAALYSTEDLIFEKIKGGLEFASCSSLEQGGACAAQSILIHDCQGLQVKHCTTAVNAEGSSANDHLGFGGGAFFVTGSLSGEKSLYMPAGDMVVANCDGAISFEGNSANFANGGAIAASGKVLFVANDKKTSFIENRALSGGAIAASSDIAFQNCAELVFKGNCAIGTEDKGSLGGGAISSLGTVLLQGNHGITCDKNESASQGGAIFGKNCQISDNEGPVVFRDSTACLGGGAIAAQEIVSIQNNQAGISFEGGKASFGGGIACGSFSSAGGASVLGTIDISKNLGAISFSRTLCTTSDLGQMEYQGGGALFGENISLSENAGVLTFKDNIVKTFASNGKILGGGAILATGKVEITNNSEGISFTGNARAPQALPTQEEFPLFSKKEGRPLSSGYSGGGAILGREVAILHNAAVVFEQNRLQCSEEEATLLGCCGGGAVHGMDSTSIVGNSSVRFGNNYAMGQGVSGGALLSKTVQLAGNGSVDFSRNIASLGGGALQASEGNCELVDNGYVLFRDNRGRVYGGAISCLRGDVVISGNKGRVEFKDNIATRLYVEETVEKVEEVEPAPEQKDNNELSFLGRAEQSFITAANQALFASEDGDLSPESSISSEELAKRRECAGGAIFAKRVRIVDNQEAVVFSNNFSDIYGGAIFTGSLREEDKLDGQIPEVLISGNAGDVVFSGNSSKRDEHLPHTGGGAICTQNLTISQNTGNVLFYNNVACSGGAVRIEDHGNVLLEAFGGDIVFKGNSSFRAQGSDAIYFAGKESHITALNATEGHAIVFHDALVFENLEERKSAEVLLINSRENPGYTGSIRFLEAESKVPQCIHVQQGSLELLNGATLCSYGFKQDAGAKLVLAAGAKLKILDSGTPVQQGHAISKPEAEIESSSEPEGAHSLWIAKNAQTTVPMVDIHTISVDLASFSSSQQEGTVEAPQVIVPGGSYVRSGELNLELVNTTGTGYENHALLKNEAKVPLMSFVASGDEASAEISNLSVSDLQIHVVTPEIEEDTYGHMGDWSEAKIQDGTLVISWNPTGYRLDPQKAGALVFNALWEEGAVLSALKNARFAHNLTAQRMEFDYSINVWGFAFGGFRTLSAENLVAIDGYKGAYGGASAGVDIQLMEDFVLGVSGAAFLGKMDSQKFDAEVSRKGVVGSVYTGFLAGSWFFKGQYSLGETQNDMKTRYGVLGESSASWTSRGVLADALVEYRSLVGPVRPTFYALHFNPYVEVSYASMKFPGFTEQGREARSFEDASLTNITIPLGMKFELAFIKGQFSEVNSLGISYAWEAYRKVEGGAVQLLEAGFDWEGAPMDLPRQELRVALENNTEWSSYFSTVLGLTAFCGGFTSTDSKLGYEANTGLRLIFSEQ ID NO: 51 - CT869 nucleotide sequenceATGAAAAAAGCGTTTTTCTTTTTCCTTATCGGAAACTCCCTATCAGGACTAGCTAGAGAGGTTCCTTCTAGAATCTTTCTTATGCCCAACTCAGTTCCAGATCCTACGAAAGAGTCGCTATCAAATAAAATTAGTTTGACAGGAGACACTCACAATCTCACTAACTGCTATCTCGATAACCTACGCTACATACTGGCTATTCTACAAAAAACTCCCAATGAAGGAGCTGCTGTCACAATAACAGATTACCTAAGCTTTTTTGATACACAAAAAGAAGGTATTTATTTTGCAAAAAATCTCACCCCTGAAAGTGGTGGTGCGATTGGTTATGCGAGTCCCAATTCTCCTACCGTGGAGATTCGTGATACAATAGGTCCTGTAATCTTTGAAAATAATACTTGTTGCAGACTATTTACATGGAGAAATCCTTATGCTGCTGATAAAATAAGAGAAGGCGGAGCCATTCATGCTCAAAATCTTTACATAAATCATAATCATGATGTGGTCGGATTTATGAAGAACTTTTCTTATGTCCAAGGAGGAGCCATTAGTACCGCTAATACCTTTGTTGTGAGCGAGAATCAGTCTTGTTTTCTCTTTATGGACAACATCTGTATTCAAACTAATACAGCAGGAAAAGGTGGCGCTATCTATGCTGGAACGAGCAATTCTTTTGAGAGTAATAACTGCGATCTCTTCTTCATCAATAACGCCTGTTGTGCAGGAGGAGCGATCTTCTCCCCTATCTGTTCTCTAACAGGAAATCGTGGTAACATCGTTTTCTATAACAATCGCTGCTTTAAAAATGTAGAAACAGCTTCTTCAGAAGCTTCTGATGGAGGAGCAATTAAAGTAACTACTCGCCTAGATGTTACAGGCAATCGTGGTAGGATCTTTTTTAGTGACAATATCACAAAAAATTATGGCGGAGCTATTTACGCTCCTGTAGTTACCCTAGTGGATAATGGCCCTACCTACTTTATAAACAATATCGCCAATAATAAGGGGGGCGCTATCTATATAGACGGAACCAGTAACTCCAAAATTTCTGCCGACCGCCATGCTATTATTTTTAATGAAAATATTGTGACTAATGTAACTAATGCAAATGGTACCAGTACGTCAGCTAATCCTCCTAGAAGAAATGCAATAACAGTAGCAAGCTCCTCTGGTGAAATTCTATTAGGAGCAGGGAGTAGCCAAAATTTAATTTTTTATGATCCTATTGAAGTTAGCAATGCAGGGGTCTCTGTGTCCTTCAATAAGGAAGCTGATCAAACAGGCTCTGTAGTATTTTCAGGAGCTACTGTTAATTCTGCAGATTTTCATCAACGCAATTTACAAACAAAAACACCTGCACCCCTTACTCTCAGTAATGGTTTTCTATGTATCGAAGATCATGCTCAGCTTACAGTGAATCGATTCACACAAACTGGGGGTGTTGTTTCTCTTGGGAATGGAGCAGTTCTGAGTTGCTATAAAAATGGTACAGGAGATTCTGCTAGCAATGCCTCTATAACACTGAAGCATATTGGATTGAATCTTTCTTCCATTCTGAAAAGTGGTGCTGAGATTCCTTTATTGTGGGTAGAGCCTACAAATAACAGCAATAACTATACAGCAGATACTGCAGCTACCTTTTCATTAAGTGATGTAAAACTCTCACTCATTGATGACTACGGGAACTCTCCTTATGAATCCACAGATCTGACCCATGCTCTGTCATCACAGCCTATGCTATCTATTTCTGAAGCTAGCGATAACCAGCTACAATCAGAAAATATAGATTTTTCGGGACTAAATGTCCCTCATTATGGATGGCAAGGACTTTGGACTTGGGGCTGGGCAAAAACTCAAGATCCAGAACCAGCATCTTCAGCAACAATCACTGATCCACAAAAAGCCAATAGATTTCATAGAACCTTACTACTAACATGGCTTCCTGCCGGGTATGTTCCTAGCCCAAAACACAGAAGTCCCCTCATAGCTAACACCTTATGGGGGAATATGCTGCTTGCAACAGAAAGCTTAAAAAATAGTGCAGAGCTGACACCTAGTGGTCATCCTTTCTGGGGAATTACAGGAGGAGGACTAGGCATGATGGTTTACCAAGATCCTCGAGAAAATCATCCTGGATTCCATATGCGCTCTTCCGGATACTCTGCGGGGATGATAGCAGGGCAGACACACACCTTCTCATTGAAATTCAGTCAGACCTACACCAAACTCAATGAGCGTTACGCAAAAAACAACGTATCTTCTAAAAATTACTCATGCCAAGGAGAAATGCTCTTCTCATTGCAAGAAGGTTTCTTGCTGACTAAATTAGTTGGGCTTTACAGCTATGGAGACCATAACTGTCACCATTTCTATACTCAAGGAGAAAATCTAACATCTCAAGGGACGTTCCGCAGTCAAACGATGGGAGGTGCTGTCTTTTTTGATCTCCCTATGAAACCCTTTGGATCAACGCATATACTGACAGCTCCCTTTTTAGGTGCTCTTGGTATTTATTCTAGCCTGTCTCACTTTACTGAGGTGGGAGCCTATCCGCGAAGCTTTTCTACAAAGACTCCTTTGATCAATGTCCTAGTCCCTATTGGAGTTAAAGGTAGCTTTATGAATGCTACCCACAGACCTCAAGCCTGGACTGTAGAATTGGCATACCAACCCGTTCTGTATAGACAAGAACCAGGGATCGCAGCCCAGCTCCTAGCCAGTAAGGGTATTTGGTTCGGTAGTGGAAGCCCCTCATCGCGTCATGCCATGTCCTATAAAATCTCACAGCAAACACAACCTTTGAGTTGGTTAACTCTCCATTTCCAGTATCATGGATTCTACTCCTCTTCAACCTTCTGTAATTATCTCAATGGGGAAATTGCTCTGCGATTCTAGSEQ ID NO: 52 - CT869 protein sequenceMKKAFFFFLIGNSLSGLAREVPSRIFLMPNSVPDPTKESLSNKISLTGDTHNLTNCYLDNLRYILAILQKTPNEGAAVTITDYLSFFDTQKEGIYFAKNLTPESGGAIGYASPNSPTVEIRDTIGPVIFENNTCCRLFTWRNPYAADKIREGGAIHAQNLYINHNHDVVGFMKNFSYVQGGAISTANTFVVSENQSCFLFMDNICIQTNTAGKGGAIYAGTSNSFESNNCDLFFINNACCAGGAIFSPICSLTGNRGNIVFYNNRCFKNVETASSEASDGGAIKVTTRLDVTGNRGRIFFSDNITKNYGGAIYAPVVTLVDNGPTYFINNIANNKGGAIYIDGTSNSKISADRHAIIFNENIVTNVTNANGTSTSANPPRRNAITVASSSGEILLGAGSSQNLIFYDPIEVSNAGVSVSFNKEADQTGSVVFSGATVNSADFHQRNLQTKTPAPLTLSNGFLCIEDHAQLTVNRFTQTGGVVSLGNGAVLSCYKNGTGDSASNASITLKHIGLNLSSILKSGAEIPLLWVEPTNNSNNYTADTAATFSLSDVKLSLIDDYGNSPYESTDLTHALSSQPMLSISEASDNQLASENIDFSGLNVPHYGWQGLWTWGWAKTQDPEPASSATITDPQKANRFHRTLLLTWLPAGYVPSPKHRSPLIANTLWGNMLLATESLKNSAELTPSGHPFWGITGGGLGMMVYQDPRENHPGFHMRSSGYSAGMIAGQTHTFSLKFSQTYTKLNERYAKNNVSSKNYSCQGEMLFSLQEGFLLTKLVGLYSYGDHNCHHFYTQGENLTSQGTFRSQTMGGAVFFDLPMKPFGSTHILTAPFLGALGIYSSLSHFTEVGAYPRSFSTKTPLINVLVPIGVKGSFMNATHRPQAWTVELAYQPVLYRQEPGIAAQLLASKGIWFGSGSPSSRHAMSYKISQQTQPLSWLTLHFQYHGFYSSSTFCNYLNGEIALRFSEQ ID NO: 53 - CT166 nucleotide sequenceGTGAACGTTCGTACGTACTCTGTTCAGAGGGGGGGGGTAAAAACGATTTCTGCTAGTGCAGTTCCTCCTACAGCAGCTGTTTTATCGAGAAAAAAGCGTGCTATAGAAGAGAAGAAGGAGGAAGCTTCTTCTGGAAAGATAGAAAATCTTGATGCTAGCAAATACGATCTTACTCCCAAGAACATAGAAGAAAAACTAGGAATTACTCCTGAACAGAAATCTACTGTTAAAGACCTATTAAATAAACTGAAAAAGGTCATTAGTGCTTACAACTCTATGCCAGATAAAAATTCGGAAGCGGGACAGAATTCCTTGATTCAACAAGGAAAATACGTCGATGCCATTCAGAAGAAGCTTCCAGCATCATCGCAGGCTCAGCCTAAACAGGCAAAAGCTAAGGAACAGAAAGCCGAAGAAAAACCTAAGACGACTCCGATTGAAGGTGTTCTTGAAACCATCAAAACAGAATTTAAAGGCCATCGTGTACCTGTTGAGAAAATCATCCATGGAATATGGATCGCAGGAGCGCCTCCGGATGGTATCGAAGATTATATGCGAGTCTTTTTAGATACTTATGAAGGTTTTGACTTCTACTTCTGGGTAGATGAGAATGCTTATGCAGCAGCTAAATTTTCTAGCATTTTGAAGAAGGTCGCTTTCGATGCGGCTATTCAAGATCTACGATCTGCCACAGATGAGTCTACGAAGGCCTTTGTTAAAGACTACGATGAATTAAAACAGAAATATGAAAAGAAAGTTGCGGAGACGACTTCTCAAGCAGAAAAAGACCAATATCTCAAAGATCTAAAGGATCTTTTAGAGAAATTTACAAAAATCAGTGATGAGATTCGTGGAAAATTTGATCGGCTGTTTCTTAAGAATGTGATTGTTGCTCAGAACGGATTCTTTAATTTCTGCTTGCTGAAAGGCCTCGGCAATATCAATGACGAAACGCGTGCAGAGTATTTAGAGAAAGAACTCAAACTTCCTACTGAGGAGATCGAACAGTATAAAAAGCTTAAAGAGACGAACAAAGAGAAGATAGCCGCTATTGTAAAACAACTAAACGAGAAACTTGGATCGGATCGGGTAAAAATCAAAGACATTAAAGAGCTGCAATCTATGAAGCAAGCTCGAAATGTCTACAATTATGAACAGGAAATGTTTCTGCGCTGGAACTATGCAGCCGCAACAGATCAGATTCGTATGTATATGTTGGAGGAACTTGGAGGTCTTTATACTGATCTGGATATGATGCCTTCATACTCTCAGGAAGTATTGGAGCTTATCAAAAAGCACAGTGATGGAAACCGAATGTTTGAGGATATGAGCTCTAGACGGGCGATTTCTGATGCGGTTTTAAAGATGGCTGTAGGTAAGGCGACAACAGTTTCCATGGAAGAGGTAGCAAAGGATATCGATGTTTCTCGCTTAACAGAAGAGGATAAGACAAAATTAAATGCTCTATTTAAGGATCTAGAGCCATTTGCAAAACCGGATTCTAAAGGAGCTGAAGCAGAAGGGGGTGAAGGAGCAAAAGGTATGAAAAAGAGCTTTTTCCAGCCCATAGATCTGAATATTGTCAGAAATACCATGCCTATCTTGAGACGCTATCATCACTATCCTGAGTTAGGATGGTTTATTCGAGGATTGAACGGATTGATGGTCTCTCATAAGGGAAGCACTGCGGTTTCTGCTGTCATTGTAGGGCAACAGGCTGCCTACCAGGAACTAGCAGCACTTAGACAAGATGTCCTTTCAGGGGAGTTTTTCCATTCTTTAGAAAATTTGACACATAGAAACCATAAGGAGCGTATTGGAAATCATCTCGTCGCTAATTATTTGGCTAAAAGTCTCTTTTTTGATTACTGCCAAGATTCAGTGATGCCGGAGGCTGTAAGTACCTTAGGTATTAGATGASEQ ID NO: 54 - CT166 protein sequenceMNVRTYSVQRGGVKTISASAVPPTAAVLSRKKRAIEEKKEEASSGKIENLDASKYDLTPKNIEEKLGITPEQKSTVKDLLNKLKKVISAYNSMPDKNSEAGQNSLIQQGKYVDAIQKKLPASSQAQPKQAKAKEQKAEEKPKTTPIEGVLETIKTEFKGHRVPVEKIIHGIWIAGAPPDGIEDYMRVFLDTYEGFDFYFWVDENAYAAAKFSSILKKVAFDAAIQDLRSATDESTKAFVKDYDELKQKYEKKVAETTSQAEKDQYLKDLKDLLEKFTKISDEIRGKFDRLFLKNVIVAQNGFFNFCLLKGLGNINDETRAEYLEKELKLPTEEIEQYKKLKETNKEKIAAIVKQLNEKLGSDRVKIKDIKELQSMKQARNVYNYEQEMFLRWNYAAATIMIRMYMLEELGGLYTDLDMMPSYSQEVLELIKKHSDGNRMFEDMSSRRAISDAVLKMAVGKATTVSMEEVAKDIDVSRLTEEDKTKLNALFKDLEPFAKPDSKGAEAEGGEGAKGMKKSFFQPIDLNIVRNTMPILRRYHHYPELGWFIRGLNGLMVSHKGSTAVSAVIVGQQAAYQELAALRQDVLSGEFFHSLENLTHRNHKERIGNHLVANYLAKSLFFDYCQDSVMPEAVSTLGIR SEQ ID NO: 55 - CT175 nucleotide sequenceATGCATCACAGGAAGTTTTTAGCAGTTTCCATTGCTTTCGTAAGTTTAGCTTTTGGGCTAACATCTTGTTATCATAAAAAAGAAGAACCAAAAGATGTTTTGCGGATTGCGATCTGTCATGATCCAATGTCTTTAGATCCGCGTCAGGTTTTTTTAAGCAAAGATGTTTCTATTGTAAAAGCTCTCTATGAAGGGTTAGTCCGGGAAAAAGAAGCTGCGTTCCAGCTAGCTTTGGCAGAAAGATATCATCAATCTGATGATGGTTGTGTTTATACTTTTTTTCTAAAAAATACATTCTGGAGCAACGGAGATGTTGTAACAGCATATGATTTTGAAGAGTCTATTAAACAAATTTATTTCCGAGAAATTGATAACCCTTCGTTACGCTCTCTTGCATTAATTAAAAATTCTCATGCTGTTTTAACAGGAGCTCTCCCTGTTGAAGATTTAGGTGTTAGAGCTTTGAATGCGAAAACTCTAGAAATTGTTTTAGAAAACCCGTTTCCTTATTTTCTAGAGATATTGGCGCACCCGGTTTTTTATCCGGTGCACACCTCTTTACGAGAATATTACAAAGATAAGCGTAACAAACGCGTTTTCCCGATAATTTCTAATGGTCCTTTTGCGATTCAATGTTATGAGCCGCAAAGATATTTACTAATCAACAAAAACCCTCTGTATCATGCCAAGCACGATGTTCTGTTAAATTCGGTATGTTTGCAGATAGTTCCTGATATCCATACAGCTATGCAGTTATTCCAAAAAAATCATATCGATTTAGTTGGGTTACCCTGGAGCTCCTCCTTTTCTTTAGAAGAACAAAGAAATCTCCCTAGAGAAAAATTATTTGATTATCCTGTATTGAGTTGCTCTGTTTTATTCTGTAACATTCATCAAACACCTTTAAATAATCCCTCGCTGAGAACAGCCCTCTCTTTAGCAATCAATCGAGAAACTTTATTAAAACTAGCAGGTAAAGGCTGTAGCGCTACGAGCTTTGTTCACCCACAATTATCTCAGATACCTGCTACTACTTTGTCTCAAGATGAGCGGATTGCTTTAGCAAAAGGCTACTTGACCGAAGCTTTAAAGACTTTATCTCAAGAAGATTTAGAAAAAATTACATTAATTTATCCTATAGAATCTGTTTGCTTACGAGCCGTTGTTCAAGAAATTCGCCAACAATTATTTGATGTACTGGGATTTAAAATTTCTACATTAGGATTAGAATATCATTGTTTTTTAGACAAACGTTCCAGAGGAGAATTCTCCTTAGCAACTGGTAATTGGATTGCAGACTATCATCAAGCTAGTGCTTTCCTGTCTGTCCTAGGTAATGGGACAAGATATAAAGACTTTCAATTGATTAACTGGCAGAACCAAAAGTACACAAATATAGTTGCTCAACTTCTGATTCAAGAATCAAGCGACCTACAGCTTATGGCAGAGCAGTTGTTGCTTAAAGAAAGTCCTCTTATTCCTCTATACCACCTCGATTATGTGTATGCGAAACAGCCTCGGGTGTCTGATCTCCAAACCTCTTCTCGTGGAGAAATTGATTTAAAAAGAGTTTCATTAGCTGAAGGATAGSEQ ID NO: 56 - CT175 protein sequenceMHHRKFLAVSIAFVSLAFGLTSCYHKKEEPKDVLRIAICHDPMSLDPRQVFLSKDVSIVKALYEGLVREKEAAFQLALAERYHQSDDGCVYTFFLKNTFWSNGDVVTAYAFEESIKQIYFREIDNPSLRSLALIKNSHAVLTGALPVEDLGVRALNAKTLEIVLENPFPYFLEILAHPVFYPVHTSLREYYKDKRNKRVFPIISNGPFAIQCYEPQRYLLINKNPLYHAKHDVLLNSVCLQIVPDIHTAMQLFQKNHIDLVGLPWSSSFSLEEQRNLPREKLFDYPVLSCSVLFCNIHQTPLNNPSLRTALSLAINRETLLKLAGKGCSATSFVHPQLSQIPATTLSQDERIALAKGYLTEALKTLSQEDLEKITLIYPIESVCLRAVVQEIRQQLFDVLGFKISTLGLEYHCFLDKRSRGEFSLATGNWIADYHQASAFLSVLGNGTRYKDFQLINWQNQKYTNIVAQLLIQESSDLQLMAEQLLLKESPLIPLYHLDYVYAKQPRVSDLQTSSRGEIDLKRVSLAEGSEQ ID NO: 57 - TC0666 nucleotide sequence (homologue of CT387)ATGAGGATTCCAATGACACTCTTTCACACTCATCACGATGCCGTCTCTCCGGACGGCTACTTATGTTCTTCCCTTCAGTTAGTTGGCTCTGGCACATATGAAGGAGAAATCGAAATCCAAAATATTCCTTCTTATTTCCTTGGATTCCGATTACCCACCCATTGCGTTCATCTTAATTTGAAGAGTTCTCTAGCCCAGTTAGGAGTAGATGCATCTCTTCTTCACTGCGAACTAAGCAAAAATCAACAACGTGCACATATGCACGTGCAGTTCACCGGCTATGGCCCTATCGCTGAGTCCATGCTATCTCTTCTCAAACCCGGAGATCGAGTAGCCAAACTGTTTGCTGCAGATGATCGTAGACTAGTCCGCTCCCCTGATTATCTTGAAAGCATGCTAAAAAATACTGATAAGACAGGACATCCTCTGCTCCGATTTGGAAAAAAACTCGAGCATCTTATCTCTTTTGATGTGGTGGACGATCGCCTCGTTGTATCACTCCCCACCTTGCCAGGCATAGTCAATTATGACCCAGACATCTATGGACTTCTTCCCTTAATTCAAAAATCACTAAGCAATCCTAAATTGAGTATTCGCCACTTCTTGTCTCTCTATCAGAAGATCGTAGAAGGACCACACATCCCTTATGAAGGAAACATTTTGTTAATCAAAACAGAGCCTCTTCATATCCGCACAGTATTTGCTCGCGTGGTCGATCAAATGCTCCCTCAAGGTCTATTTCACACTTCTGCCAACATTTTAGAACCCACAACGCGAGAGTCTGGAGATATTTTTGAATTTTTTGGAAATCCCTCCACTCTTGTAGAAAGAATCCCTCTAGAATTCTTCACTATCGAACCCTACAAAGAACACTCTTACTTCTGTAATCGAGATCTATTGCAAACTACCTTGCAATCGGAAAGTGAAATCAAAAAAATATTCGATACAGCTCCTCAAGAGCCTGTAAAAGCCGCCACTTATTTATCAAAAGGAAGTGAAATTTCTTCTCTTGATGCAGATTCTTGGCTTACGGGATCCGCAGCTGCATACCAATGTAGCGAAAAACAGGCAGCTAAAGACGAATACATCCACGCTCAACCCTGTTATCCATTTTTGGAAGCAATGGAAACGGGACTCATCAATAGCGAAGGAGCTTTACTCACTCGGTTTTTCCCCTCTTCCAGCTTAAAAGGGATGTTGATCTCCTATCATGTACGCCACTATCTTAAGCAAATTTACTTTCAAGTTCCTTCTTATACATATGGAGACTACTTCTCTCATAATGACCGAGGATTACTGTTAGATCTATATCAGGCGAACATTGATGTGTTCTGGGCTGATGAAGAGAGCGGCCGTGTATTGCAATATACAAAACGGCGCGACAAAAATAGTGGAATGTTCGTCGTTAAAAATCGAGTAGAAGAGTTCCAATCAGCATATTTCGTAGCGATTTATGGATCACGTCTCCTGGAAAATAATTTCTCGGCCCAACTAAACACGCTTCTTGCAGGGTTACAAAAAGCTGCACACACTCTAGGCATTCCAGGCTTCTCAAAACCCACTCCTCTTGCCGTAATCACAGGAGGAGGGACTGGCGTTATGGCTACAGGAAATCGTGTTGCAAAAGAGTTGGGAATTCTTTCTTGCGGGACCGTTCTCGATTTGGAAGCTTCACCTGCACAAATAGATCAGCCTGCAAACGAATTTTTAGATGCCAAAATGACATACCGTCTACCGCAACTTATAGAAAGACAAGAACATTTTTATTCAGACCTTGCCATTTTAGTTGTTGGTGGTGTTGGAACAGATTTCGAACTTTACCTAGAACTCGTCTACTTGAAAACAGGCGCCAAACCTCCTACTCCAATTTTCCTTATTGGGCCTGTTGAATACTGGAAAGAGAAAGTTGCTCATGCCTATGAGATTAATCTTAAAGCAGGAACTATTCGTGGTTCTGAGTGGATCAGCAACTGCTTATTCTGCATTACATCTCCTGAAGCAGGAATTGCTGTATTCGAACAGTTCCTCGCTGGAGAACTTCCCATAGGATATGATTATCCTCCAGCTCCAGACGGATTAGTTATCGTCTAASEQ ID NO: 58 - TC0666 protein sequence (homologue of CT387)MRIPMTLFHTHHDAVSPDGYLCSSLQLVGSGTVEGEIEIQNIPSYFLGFRLPTHCVHLNLKSSLAQLGVDASLLHCELSKNQQRAHMHVQFTGYGPIAESMLSLLKPGDRVAKLFAADDRRLVRSPDYLESMLKNTDKTGHPLLRFGKKLEHLISFDVVDDRLVVSLPTLPGIVNYDPDIYGLLPLIQKSLSNPKLSIRHFLSLYQKIVEGPHIPYEGNILLIKTEPLHIRTVFARVVDQMLPQGLFHTSANILEPTTRESGDIFEFFGNPSTLVERIPLEFFTIEPYKEHSYFCNRDLLQTTLQSESEIKKIFDTAPQEPVKAATYLSKGSEISSLDADSWLTGSAAAYQCSEKQAAKDEYIHAQPCYPFLEAMETGLINSEGALLTRFFPSSSLKGMLISYHVRHYLKQIYFQVPSYTYGDYFSHNDRGLLLDLYQANIDVFWADEESGRVLQYTKRRDKNSGMFVVKNRVEEFQSAYFVAIYGSRLLENNFSAQLNTLLAGLQKAAHTLGIPGFSKPTPLAVITGGGTGVMATGNRVAKELGILSCGTVLDLEASPAQIDQPANEFLDAKMTYRLPQLIERQEHFYSDLAILVVGGVGTDFELYLELVYLKTGAKPPTPIFLIGPVEYWKEKVAHAYEINLKAGTIRGSEWISNCLFCITSPEAGIAVFEQFLAGELPIGYDYPPAPDGLVIV SEQ ID NO: 59 - TC0197 nucleotide sequenceATGAGTTCCGAGAAAGATAAAAAAAACTCCTGTTCTAAGTTTTCCTTATCGGTAGTAGCAGCTATTCTCGCTTCTATGAGTGGTTTATCGAATTGTTCCGATCTTTATGCCGTAGGAAGTTCTGCAGACCATCCTGCCTACTTGATTCCTCAAGCGGGGTTATTATTGGATCATATTAAGGATATATTCATTGGCCCTAAAGATAGTCAGGATAAGGGGCAGTATAAGTTGATTATTGGTGAGGCTGGCTCTTTCCAAGATAGTAATGCAGAGACTCTTCCTCAAAAGGTAGAGCACAGCACTTTGTTTTCAGTTACAACACCTATAATTGTGCAAGGAATAGATCAACAAGATCAGGTCTCTTCGCAGGGATTGGTCTGTAATTTTTCAGGAGATCATTCAGAGGAGATTTTTGAGAGAGAATCCTTTTTAGGGATCGCTTTCCTAGGGAATGGTAGCAAGGATGGAATCACGTTAACAGATATAAAATCTTCGTTATCTGGTGCTGCCTTGTATTCTTCAGATGATCTTATTTTTGAAAGAATTAAGGGAGATATAGAGCTTTCTTCTTGTTCATCTTTAGAAAGAGGAGGAGCTTGTTCAGCTCAAAGTATTTTAATTCATGATTGTCAAGGATTAACGGTAAAACATTGTGCCGCAGGGGTGAATGTTGAAGGAGTTAGTGCTAGCGACCATCTCGGATTTGGGGGCGGGGCCTTCTCTACTACAAGTTCTCTTTCTGGAGAGAAGAGTTTGTATATGCCTGCAGGCGATATTGTGGTGGCTACCTGCGATGGTCCTGTGTGTTTCGAAGGAAATAGTGCTCAGTTAGCAAATGGTGGCGCTATTGCCGCTTCTGGTAAAGTTCTTTTTGTAGCTAACGAAAAAAAGATTTCCTTTACAGACAACCAAGCTTTGTCTGGAGGAGCTATTTCTGCATCTTCTAGTATTTCTTTCCAAAATTGTGCTGAGCTTGTGTTCAAGAGTAATCTTGCAAAAGGAGTTAAAGATAAATGTTCTTTGGGAGGAGGTGCTTTAGCCTCTTTAGAATCCGTAGTTTTGAAAGATAATCTCGGTATTACTTATGAAAAAAATCAGTCCTATTCGGAAGGAGGGGCTATTTTTGGGAAGGATTGTGAGATTTTTGAAAACAGGGGGCCTGTTGTATTCAGAGATAATACAGCTGCTTTAGGAGGCGGAGCTATTTTGGCGCAACAAACTGTGGCGATTTGTGGTAATAAGTCTGGAATATCTTTTGAAGGAAGTAAGTCTAGTTTTGGAGGGGCCATTGCTTGTGGAAATTTCTCTTCTGAGAATAATTCTTCAGCTTTGGGATCAATTGATATCTCTAACAATCTAGGAGATATCTCTTTTCTTCGGACTCTGTGTACTACTTCGGATTTAGGGCAAACGGATTACCAAGGGGGAGGGGCCTTATTCGCTGAAAATATTTCTCTTTCTGAGAATGCTGGTGCAATTACTTTCAAAGACAATATTGTGAAGACATTTGCCTCAAATGGAAAAATGTTGGGTGGAGGGGCAATTTTAGCTTCAGGAAATGTTTTGATTAGCAAAAACTCTGGAGAGATTTCTTTTGTAGGGAATGCTCGAGCTCCTCAGGCTATTCCGACTCGTTCATCTGACGAATTGTCTTTTGGCGCACAATTAACTCAAACTACTTCAGGATGTTCTGGAGGAGGAGCTCTTTTTGGTAAAGAGGTTGCCATTGTTCAAAATGCCACTGTTGTATTCGAGCAAAATCGCTTACAGTGTGGCGAGCAGGAAACACATGGTGGAGGCGGTGCTGTTTATGGTATGGAGAGTGCCTCTATTATTGGAAACTCTTTTGTGAGATTCGGAAATAATTACGCTGTAGGGAATCAGATTTCTGGAGGAGCTCTTTTATCCAAGAAGGTCCGTTTAGCTGAAAATACAAGGGTAGATTTTTCTCGAAATATCGCTACTTTCTGCGGCGGGGCTGTTCAAGTTTCTGATGGAAGTTGCGAATTGATCAACAATGGGTATGTGCTATTCAGAGATAACCGAGGGCAGACATTTGGTGGGGCTATTTCTTGCTTGAAAGGAGATGTGATCATTTCCGGAAATAAAGATAGGGTTGAGTTTAGAGATAACATTGTGACGCGGCCTTATTTTGAAGAAAATGAAGAAAAAGTTGAGACAGCAGATATTAATTCAGATAAGCAAGAAGCAGAAGAGCGCTCTTTATTAGAGAACATTGAGCAGAGCTTTATTACTGCAACTAATCAGACCTTTTTCTTAGAGGAAGAGAAACTCCCATCAGAAGCTTTTATCTCTGCTGAAGAACTTTCAAAGAGAAGAGAATGTGCTGGTGGGGCGATTTTTGCAAAACGGGTCTACATTACGGATAATAAAGAACCTATCTTGTTTTCGCATAATTTTTCTGATGTTTATGGGGGAGCTATTTTTACGGGTTCTCTACAGGAAACTGATAAACAAGATGTTGTAACTCCTGAAGTTGTGATATCAGGCAACGATGGGGATGTCATTTTTTCTGGAAATGCAGCTAAACATGATAAGCATTTACCTGATACAGGTGGTGGAGCCATTTGTACACAGAATTTGACGATTTCCCAAAACAATGGGAATGTCTTGTTCTTGAACAATTTTGCTTGTTCTGGTGGAGCAGTTCGCATAGAGGATCATGGAGAAGTTCTTTTAGAGGCTTTTGGGGGAGATATTATTTTCAATGGAAACTCTTCTTTCAGAGCTCAAGGATCGGATGCGATCTATTTTGCTGGTAAGGACTCTAGAATTAAAGCTTTAAATGCTACTGAAGGACATGCGATTGTGTTCCAAGATGCATTGGTGTTTGAAAATATAGAAGAAAGAAAGTCTTCGGGACTATTGGTGATTAACTCTCAGGAAAATGAGGGTTATACGGGATCCGTCCGATTTTTAGGATCTGAAAGTAAGGTTCCTCAATGGATTCATGTGCAACAGGGAGGTCTTGAGTTGCTACATGGAGCTATTTTATGTAGTTATGGGGTTAAACAAGATCCTAGAGCTAAAATAGTATTATCTGCTGGATCTAAATTGAAGATTCTAGATTCAGAGCAAGAAAATAACGCAGAAATTGGAGATCTTGAAGATTCTGTTAATTCAGAAAAAACACCATCTCTTTGGATTGGGAAGAACGCTCAAGCAAAAGTCCCTCTGGTTGATATCCATACTATTTCTATTGATTTAGCATCATTTTCTTCTAAAGCTCAGGAAACCCCTGAGGAAGCTCCACAAGTCATCGTCCCTAAGGGAAGTTGTGTCCACTCGGGAGAGTTAAGTTTGGAGTTGGTTAATACAACAGGAAAAGGTTATGAGAATCATGCGTTGTTAAAAAATGATACTCAGGTTTCTCTCATGTCTTTCAAAGAGGAAAATGATGGATCTTTAGAAGATTTGAGTAAGTTGTCTGTTTCGGATTTACGCATTAAAGTTTCTACTCCAGATATTGTAGAAGAAACTTATGGCCATATGGGGGATTGGTCTGAAGCTACAATTCAAGATGGGGCTCTTGTCATTAATTGGCATCCTACTGGATATAAATTAGATCCGCAAAAAGCTGGTTCTTTGGTATTCAATGCATTATGGGAGGAAGAGGCTGTATTGTCTACTCTAAAAAATGCTCGGATTGCCCATAACCTTACCATTCAGAGAATGGAATTTGATTATTCTACAAATGCTTGGGGATTAGCTTTTAGTAGCTTTAGAGAGCTATCTTCAGAGAAGCTTGTTTCTGTTGATGGATATAGAGGCTCTTATATAGGGGCTTCTGCAGGCATTGATACTCAGTTGATGGAAGATTTTGTTTTGGGAATCAGCACGGCTTCCTTCTTCGGGAAAATGCATAGTCAGAATTTTGATGCAGAGATTTCTCGACATGGTTTTGTTGGTTCGGTCTATACAGGCTTCCTAGCTGGGGCCTGGTTCTTCAAGGGGCAGTACAGTCTTGGCGAAACACATAACGATATGACAACTCGTTACGGGGTTTTGGGAGAATCTAATGCTACTTGGAAGTCTCGAGGAGTACTAGCAGATGCTTTAGTTGAATATCGTAGTTTAGTCGGTCCAGCACGACCTAAATTTTATGCTTTGCATTTTAATCCTTATGTCGAGGTATCTTATGCATCTGCGAAGTTCCCTAGTTTTGTAGAACAAGGAGGAGAAGCTCGTGCTTTTGAAGAAACCTCTTTAACAAACATTACCGTTCCCTTTGGTATGAAATTTGAACTATCTTTTACAAAAGGACAGTTTTCAGAGACTAATTCTCTTGGAATAGGTTGTGCATGGGAAATGTATCGGAAAGTCGAAGGAAGATCTGTAGAGCTACTAGAAGCTGGTTTTGATTGGGAAGGATCTCCTATAGATCTCCCTAAACAAGAGCTGAGAGTGGCTTTAGAAAACAATACGGAATGGAGTTCGTATTTTAGTACAGCTCTAGGAGTAACAGCATTTTGTGGAGGATTTTCTTCTATGGATAATAAACTAGGATACGAAGCGAATGCTGGAATGCGTTTGATTTTCTAG SEQ ID NO: 60 - TC0197 protein sequenceMSSEKDKKNSCSKFSLSVVAAILASMSGLSNCSDLYAVGSSADHPAYLIPQAGLLLDHIKDIFIGPKDSQDKGQYKLIIGEAGSFQDSNAETLPQKVEHSTLFSVTTPIIVQGIDQQDQVSSQGLVCNFSGDHSEEIFERESFLGIAFLGNGSKDGITLTDIKSSLSGAALYSSDDLIFERIKGDIELSSCSSLERGGACSAQSILIHDCQGLTVKHCAAGVNVEGVSASDHLGFGGGAFSTTSSLSGEKSLYMPAGDIVVATCDGPVCFEGNSAQLANGGAIAASGKVLFVANEKKISFTDNQALSGGAISASSSISFQNCAELVFKSNLAKGVKDKCSLGGGALASLESVVLKDNLGITYEKNQSYSEGGAIFGKDCEIFENRGPVVFRDNTAALGGGAILAQQTVAICGNKSGISFEGSKSSFGGAIACGNFSSENNSSALGSIDISNNLGDISFLRTLCTTSDLGQTDYQGGGALFAENISLSENAGAITFKDNIVKTFASNGKMLGGGAILASGNVLISKNSGEISFVGNARAPQAIPTRSSDELSFGAQLTQTTSGCSGGGALFGKEVAIVQNATVVFEQNRLQCGEQETHGGGGAVYGMESASIIGNSFVRFGNNYAVGNQISGGALLSKKVRLAENTRVDFSRNIATFCGGAVQVSDGSCELINNGYVLFRDNRGQTFGGAISCLKGDVIISGNKDRVEFRDNIVIRPYFEENEEKVETADINSDKQEAEERSLLENIEQSFITATNQTFFLEEEKLPSEAFISAEELSKRRECAGGAIFAKRVYITDNKEPILFSHNFSDVYGGAIFTGSLQETDKQDVVTPEVVISGNDGDVIFSGNAAKHDKHLPDTGGGAICTQNLTISQNNGNVLFLNNFACSGGAVRIEDHGEVLLEAFGGDIIFNGNSSFRAQGSDAIYFAGKDSRIKALNATEGHAIVFQDALVFENIEERKSSGLLVINSQENEGYTGSVRFLGSESKVPQWIHVQQGGLELLHGAILCSYGVKQDPRAKIVLSAGSKLKILDSEQENNAEIGDLEDSVNSEKTPSLWIGKNAQAKVPLVDIHTISIDLASFSSKAQETPEEAPQVIVPKGSCVHSGELSLELVNTTGKGYENHALLKNDTQVSLMSFKEENDGSLEDLSKLSVSDLRIKVSTPDIVEETYGHMGDWSEATIQDGALVINWHPTGYKLDPQKAGSLVFNALWEEEAVLSTLKNARIAHNLTIQRMEFDYSTNAWGLAFSSFRELSSEKLVSVDGYRGSYIGASAGIDTQLMEDFVLGISTASFFGKMHSQNFDAEISRHGFVGSVYTGFLAGAWFFKGQYSLGETHNDMTTRYGVLGESNATWKSRGVLADALVEYRSLVGPARPKFYALHFNPYVEVSYASAKFPSFVEQGGEARAFEETSLTNITVPFGMKFELSFTKGQFSETNSLGIGCAWEMYRKVEGRSVELLEAGFDWEGSPIDLPKQELRVALENNTEWSSYFSTALGVTAFCGGFSSMDNKLGYEANAGMRLIFSEQ ID NO: 61 - TC0261 nucleotide sequenceATGAAAAAACTGTTCTTTTTTGTCCTTATTGGAAGCTCTATACTGGGATTTACTCGAGAAGTCCCTCCTTCGATTCTTTTAAAGCCTATACTAAATCCATACCATATGACCGGGTTATTTTTTCCCAAGGTTAATTTGCTTGGAGACACACATAATCTCACTGATTACCATTTGGATAATCTAAAATGCATTCTGGCTTGCCTACAAAGAACTCCTTATGAAGGAGCTGCTTTCACAGTAACCGATTACTTAGGTTTTTCAGATACACAAAAGGATGGTATTTTTTGTTTTAAAAATCTTACTCCAGAGAGTGGAGGGGTTATTGGTTCCCCAACTCAAAACACTCCTACTATAAAAATTCATAATACAATCGGCCCCGTTCTTTTCGAAAATAATACCTGTCATAGACTGTGGACACAGACCGATCCCGAAAATGAAGGAAACAAAGCACGCGAAGGCGGGGCAATTCATGCTGGGGACGTTTACATAAGCAATAACCAGAACCTTGTCGGATTCATAAAGAACTTTGCTTATGTTCAAGGTGGAGCTATTAGTGCTAATACTTTTGCCTATAAAGAAAATAAATCGAGCTTTCTTTGCCTAAATAACTCTTGTATACAAACTAAGACGGGAGGGAAAGGTGGTGCTATTTACGTTAGTACGAGCTGCTCTTTCGAGAACAATAACAAGGATCTGCTTTTCATCCAAAACTCCGGCTGTGCAGGAGGAGCTATCTTCTCTCCAACCTGTTCTCTAATAGGAAACCAAGGAGATATTGTTTTTTACAGCAACCACGGTTTTAAAAATGTTGATAATGCAACTAACGAATCTGGGGATGGAGGAGCTATTAAAGTAACTACCCGCTTGGACATCACCAATAATGGTAGTCAAATCTTTTTTTCTGATAATATCTCAAGAAATTTTGGAGGAGCTATTCATGCTCCTTGTCTTCATCTTGTTGGTAATGGGCCAACCTATTTTACAAACAATATAGCTAATCACACAGGTGGGGCTATTTATATAACAGGAACAGAAACCTCAAAGATTTCTGCAGATCACCATGCTATTATTTTTGATAATAACATTTCTGCAAACGCCACCAATGCGGACGGATCTAGCAGCAACACTAATCCTCCTCACAGAAATGCGATCACTATGGACAATTCCGCTGGAGGAATAGAACTTGGTGCAGGGAAGAGCCAGAATCTTATTTTCTATGATCCTATTCAAGTGACGAATGCTGGAGTTACCGTAGACTTCAATAAGGATGCCTCCCAAACCGGATGTGTAGTTTTCTCTGGAGCGACTGTCCTTTCTGCAGATATTTCTCAGGCTAATTTGCAAACTAAAACACCTGCAACGCTTACTCTCAGTCACGGTCTTCTGTGTATCGAAGATCGTGCTCAGCTCACAGTGAACAATTTTACACAAACAGGAGGGATTGTAGCCTTAGGAAATGGAGCAGTTTTAAGCAGCTACCAACACAGCACTACAGACGCCACTCAAACTCCCCCTACAACCACCACTACAGATGCTTCCGTAACTCTTAATCACATTGGATTAAATCTCCCCTCTATTCTTAAGGATGGAGCAGAGATGCCTCTATTATGGGTAGAACCTATAAGCACAACTCAAGGTAACACTACAACATATACGTCAGATACCGCGGCTTCCTTCTCATTAAATGGAGCCACACTCTCTCTCATTGATGAAGATGGAAATTCTCCCTATGAAAACACGGACCTCTCTCGTGCATTGTACGCTCAACCTATGCTAGCAATTTCTGAGGCCAGTGATAACCAATTGCAATCCGAAAGCATGGACTTTTCTAAAGTTAATGTTCCTCACTATGGATGGCAAGGACTTTGGACCTGGGGGTGGGCAAAAACTGAAAATCCAACAACAACTCCTCCAGCAACAATTACTGATCCGAAAAAAGCTAATCAGTTTCATAGAACTTTATTATTAACGTGGCTCCCTGCTGGTTATATCCCCAGCCCTAAACATAAAAGCCCTTTAATAGCTAATACCTTGTGGGGGAATATACTTTTTGCAACGGAAAACTTAAAAAATAGCTCAGGGCAAGAACTTCTTGATCGTCCTTTCTGGGGAATTACAGGAGGGGGCTTGGGGATGATGGTCTATCAAGAACCTAGAAAAGACCATCCTGGATTCCACATGCATACCTCCGGATATTCAGCAGGAATGATTACAGGAAACACACATACCTTCTCATTACGATTCAGCCAGTCCTATACAAAACTCAATGAACGTTATGCCAAGAACTATGTGTCTTCTAAAAATTACTCTTGCCAAGGGGAAATGCTTTTGTCCTTACAAGAAGGACTCATGCTGACTAAACTAATTGGTCTCTATAGTTATGGGAATCACAACAGCCACCATTTCTATACCCAAGGAGAAGACCTATCGTCTCAAGGGGAGTTCCATAGTCAGACTTTTGGAGGGGCTGTCTTTTTTGATCTACCTCTGAAACCTTTTGGAAGAACACACATACTTACAGCTCCTTTCTTAGGTGCCATTGGTATGTATTCTAAGCTGTCTAGCTTTACAGAAGTAGGAGCCTATCCAAGAACCTTTATTACAGAAACGCCTTTAATCAATGTCCTGATTCCTATCGGAGTAAAAGGTAGCTTCATGAATGCCACCCATAGACCTCAGGCCTGGACTGTAGAGCTTGCTTACCAACCTGTTCTTTACAGACAAGAACCTAGTATCTCTACCCAATTACTCGCTGGTAAAGGTATGTGGTTTGGGCATGGAAGTCCTGCATCTCGCCACGCTCTAGCTTATAAAATTTCACAGAAAACACAGCTTTTGCGATTTGCAACACTTCAACTCCAGTATCACGGATACTATTCGTCTTCCACTTTCTGTAATTATCTGAATGGAGAGGTATCTTTACGTTTCTAA SEQ ID NO: 62 - TC0261 protein sequenceMKKLFFFVLIGSSILGFTREVPPSILLKPILNPYHMTGLFFPKVNLLGDTHNLTDYHLDNLKCILACLQRTPYEGAAFTVTDYLGFSDTQKDGIFCFKNLTPESGGVIGSPTQNTPTIKIHNTIGPVLFENNTCHRLWTQTDPENEGNKAREGGAIHAGDVYISNNQNLVGFIKNFAYVQGGAISANTFAYKENKSSFLCLNNSCIQTKTGGKGGAIYVSTSCSFENNNKDLLFIQNSGCAGGAIFSPTCSLIGNQGDIVFYSNHGFKNVDNATNESGDGGAIKVTTRLDITNNGSQIFFSDNISRNFGGAIHAPCLHLVGNGPTYFTNNIANHTGGAIYITGTETSKISADHHAIIFDNNISANATNADGSSSNTNPPHRNAITMDNSAGGIELGAGKSQNLIFYDPIQVTNAGVTVDFNKDASQTGCVVFSGATVLSADISQANLQTKTPATLTLSHGLLCIEDRAQLTVNNFTQTGGIVALGNGAVLSSYQHSTTDATQTPPTTTTTDASVTLNHIGLNLPSILKDGAEMPLLWVEPISTTQGNTTTYTSDTAASFSLNGATLSLIDEDGNSPYENTDLSRALYAQPMLAISEASDNQLQSESMDFSKVNVPHYGWQGLWTWGWAKTENPTTTPPATITDPKKANQFHRTLLLTWLPAGYIPSPKHKSPLIANTLWGNILFATENLKNSSGQELLDRPFWGITGGGLGMMVYQEPRKDHPGFHMHTSGYSAGMITGNTHTFSLRFSQSYTKLNERYAKNYVSSKNYSCQGEMLLSLQEGLMLTKLIGLYSYGNHNSHHFYTQGEDLSSQGEFHSQTFGGAVFFDLPLKPFGRTHILTAPFLGAIGMYSKLSSFTEVGAYPRTFITETPLINVLIPIGVKGSFMNATHRPQAWTVELAYQPVLYRQEPSISTQLLAGKGMWFGHGSPASRHALAYKISQKTQLLRFATLQLQYHGYYSSSTFCNYLNGEVSLRFSEQ ID NO: 63 - CT733 fragment nucleotide sequenceGCACCTCAACCTCGCGGAACGCTTCCTAGCTCGACCACAAAAATTGGATCAGAAGTTTGGATTGAACAAAAAGTCCGCCAATATCCAGAGCTTTTATGGTTAGTAGAGCCGTCCTCTACGGGAGCCTCTTTAAAATCTCCTTCAGGAGCCATCTTTTCTCCAACATTATTCCAAAAAAAGGTCCCTGCTTTCGATATCGCAGTGCGCAGTTTGATTCACTTACATTTATTAATCCAGGGTTCCCGCCAAGCCTATGCTCAACTGATCCAACTACAGACCAGCGAATCCCCTCTAACATTTAAGCAATTCCTTGCATTGCATAAGCAATTAACTCTATTTTTAAATTCCCCTAAGGAATTTTATGACTCTGTTAAAGTGTTAGAGACAGCTATCGTCTTACGTCACTTAGGCTGTTCAACTAAGGCTGTTGCTGCGTTTAAACCTTATTTCTCAGAAATGCAAAGAGAGGCTTTTTACACTAAGGCTCTGCATGTACTACACACCTTCCCAGAGCTAAGCCCATCATTTGCTCGCCTCTCTCCGGAGCAGAAAACTCTCTTCTTCTCCTTGAGAAAATTGGCGAATTACGATGAGTTACTCTCGCTGACGAACACCCCAAGTTTTCAGCTTCTGTCTGCTGGGCGCTCGCAACGAGCTCTTTTAGCTCTGGACTTGTACCTCTATGCTTTGGATTCCTGTGGAGAACAGGGGATGTCCTCTCAATTCCACACAAACTTCGCACCTCTACAGTCCATGTTGCAACAATACGCTACTGTAGAAGAGGCCTTTTCTCGTTATTTTACTTACCGAGCTAATCGATTAGGATTTGATGGCTCTTCTCGATCCGAGATGGCTTTAGTAAGAATGGCCACCTTGATGAACTTGTCTCCTTCCGAAGCTGCGATTTTAACCACAAGCTTCAAAACCCTTCCTACAGAAGAAGCGGATACTTTGATCAATAGTTTCTATACCAATAAGGGCGATTCGTTGGCTCTTTCTCTGCGAGGGTTGCCTACACTTGTATCCGAACTGACGCGAACTGCCCATGGCAATACCAATGCAGAAGCTCGATCTCAGCAAATTTATGCAACTACCCTATCGCTAGTAGTAAAGAGTCTGAAAGCGCACAAAGAAATGCTAAACAAGCAAATTCTTTCTAAGGAAATTGTTTTAGATTTCTCAGAAACTGCAGCTTCTTGCCAAGGATTGGATATCTTTTCCGAGAATGTCGCTGTTCAAATTCACTTAAATGGAACCGTTAGTATCCATTTASEQ ID NO: 64 - CT733 fragment protein sequenceAPQPRGILPSSTTKIGSEVWIEQKVRQYPELLWLVEPSSTGASLKSPSGAIFSPTLFQKKVPAFDIAVRSLIHLHLLIQGSRQAYAQLIQLQTSESPLTFKQFLALHKQLTLFLNSPKEFYDSVKVLETAIVLRHLGCSTKAVAAFKPYFSEMQREAFYTKALHVLHTFPELSPSFARLSPEQKTLFFSLRKLANYDELLSLTNTPSFQLLSAGRSQRALLALDLYLYALDSCGEQGMSSQFHTNFAPLQSMLQQYATVEEAFSRYFTYRANRLGFDGSSRSEMALVRMATLMNLSPSEAAILTTSFKTLPTEEADTLINSFYTNKGDSLALSLRGLPTLVSELTRTAHGNTNAEARSQQIYATTLSLVVKSLKAHKEMLNKQILSKEIVLDFSETAASCQGLDIFSENVAVQIHLNGTVSIHLSEQ ID NO: 65 - CT153 fragment nucleotide sequenceACTAAGCCTTCTTTCTTATACGTTATTCAACCTTTTTCCGTATTTAATCCACGATTAGGACGTTTCTCTACAGACTCAGATACTTATATCGAAGAAGAAAACCGCCTAGCATCGTTCATTGAGAGTTTGCCACTGGAGATCTTCGATATACCTTCTTTCATGGAAACCGCGATTTCCAATAGCCCCTATATTTTATCTTGGGAGACAACTAAAGACGGCGCTCTGTTCACTATTCTTGAACCCAAACTCTCAGCTTGCGCAGCCACTTGCCTGGTAGCCCCTTCTATACAAATGAAATCCGATGCGGAGCTCCTAGAAGAAATTAAGCAAGCGTTATTACGCAGCTCTCATGACGGTGTGAAATATCGCATCACCAGAGAATCCTTCTCTCCAGAAAAGAAAACTCCTAAGGTTGCTCTAGTCGATGACGATATTGAATTGATTCGCAATGTCGACTTTTTGGGTAGAGCTGTTGACATTGTCAAATTAGACCCTATTAATATTCTGAATACCGTAAGCGAAGAGAATATTCTAGATTACTCTTTTACAAGAGAAACGGCTCAGCTGAGCGCGGATGGTCGTTTTGGTATTCCTCCAGGGACTAAGCTATTCCCTAAACCTTCTTTTGATGTAGAAATCAGTACCTCCATTTTCGAAGAAACAACTTCATTTACTCGAAGTTTTTCTGCATCGGTTACTTTTAGTGTACCAGACCTCGCGGCGACTATGCCTCTTCAAAGCCCTCCCATGGTAGAAAATGGTCAAAAAGAAATTTGTGTCATTCAAAAACACTTATTCCCAAGCTACTCTCCTAAACTAGTCGATATTGTTAAACGATACAAAAGAGAGGCTAAGATCTTGATTAACAAGCTTGCCTTTGGAATGTTATGGCGACATCGGGCTAAAAGCCAAATCCTCACCGAGGGAAGCGTACGTCTAGACTTACAAGGATTCACAGAATCGAAGTACAATTACCAGATTCAAGTAGGATCCCATACGATTGCAGCTGTATTAATCGATATGGATATTTCCAAGATTCAATCCAAATCAGAACAAGCTTATGCAATTAGGAAAATCAAATCAGGCTTTCAACGTAGCTTGGATGACTATCATATTTATCAAATTGAAAGAAAACAAACCTTTTCTTTTTCTCCGAAGCATCGCAGCCTCTCATCCACATCCCATTCCGAAGATTCTGATTTGGATCTTTCTGAAGCAGCCGCCTTTTCAGGAAGTCTTACCTGCGAGTTTGTAAAAAAAAGCACTCAACATGCCAAGAATACCGTCACATGTTCCACAGCCGCTCATTCCCTATACACACTCAAAGAAGATGACAGCTCGAACCCCTCTGAAAAACGATTAGATAGTTGTTTCCGCAATTGGATTGAAAACAAACTAAGCGCCAATTCTCCAGATTCCTGGTCAGCGTTTATTCAAAAATTCGGAACACACTATATTGCATCAGCAACTTTTGGAGGGATAGGTTTCCAAGTGCTCAAACTATCTTTTGAACAGGTGGAGGATCTACATAGCAAAAAGATCTCCTTAGAAACCGCAGCAGCCAACTCTCTATTAAAAGGTTCTGTATCCAGCAGCACAGAATCTGGATACTCCAGCTATAGCTCCACGTCTTCTTCTCATACGGTATTTTTAGGAGGAACGGTCTTACCTTCGGTTCATGATGAACGTTTAGACTTTAAAGATTGGTCGGAAAGTGTGCACCTGGAACCTGTTCCTATCCAGGTTTCTTTACAACCTATAACGAATTTACTAGTTCCTCTCCATTTTCCTAATATCGGTGCTGCAGAGCTCTCTAATAAACGAGAATCTCTTCAACAAGCGATTCGAGTCTATCTCAAAGAACATAAAGTAGATGAGCAAGGAGAACGTACTACATTTACATCAGGAATCGATAATCCTTCTTCCTGGTTTACCTTAGAAGCTGCCCACTCTCCTCTTATAGTCAGTACTCCTTACATTGCTTCGTGGTCTACGCTTCCTTATTTGTTCCCAACATTAAGAGAACGTTCTTCGGCAACCCCTATCGTTTTCTATTTTTGTGTAGATAATAATGAACATGCTTCGCAAAAAATATTAAACCAATCGTATTGCTTCCTCGGGTCCTTGCCTATTCGACAAAAAATTTTTGGTAGCGAATTTGCTAGTTTCCCCTATCTATCTTTCTATGGAAATGCAAAAGAGGCGTACTTTGATAACACGTACTACCCAACGCGTTGTGGGTGGATTGTTGAAAAGTTAAATACTACACAAGATCAATTCCTCCGGGATGGAGACGAGGTGCGACTAAAACATGTTTCCAGCGGAAAGTATCTAGCAACAACTCCTCTTAAGGATACCCATGGTACACTCACGCGTACAACGAACTGTGAAGATGCTATCTTTATTATTAAAAAATCTTCAGGTTATSEQ ID NO: 66 - CT153 fragment protein sequenceTKPSFLYVIQPFSVFNPRLGRFSTDSDTYIEEENRLASFIESLPLEIFDIPSFMETAISNSPYILSWETTKDGALFTILEPKLSACAATCLVAPSIQMKSDAELLEEIKQALLRSSHDGVKYRITRESFSPEKKTPKVALVDDDIELIRNVDFLGRAVDIVKLDPINILNTVSEENILDYSFTRETAQLSADGRFGIPPGTKLFPKPSFDVEISTSIFEETTSFTRSFSASVTFSVPDLAATMPLQSPPMVENGQKEICVIQKHLFPSYSPKLVDIVKRYKREAKILINKLAFGMLWRHRAKSQILTEGSVRLDLQGFTESKYNYQIQVGSHTIAAVLIDMDISKIQSKSEQAYAIRKIKSGFQRSLDDYHIYQIERKQTFSFSPKHRSLSSTSHSEDSDLDLSEAAAFSGSLTCEFVKKSTQHAKNTVTCSTAAHSLYTLKEDDSSNPSEKRLDSCFRNWIENKLSANSPDSWSAFIQKFGTHYIASATFGGIGFQVLKLSFEQVEDLHSKKISLETAAANSLLKGSVSSSTESGYSSYSSTSSSHTVFLGGTVLPSVHDERLDFKDWSESVHLEPVPIQVSLQPITNLLVPLHFPNIGAAELSNKRESLQQAIRVYLKEHKVDEQGERTTFTSGIDNPSSWFTLEAAHSPLIVSTPYIASWSTLPYLFPTLRERSSATPIVFYFCVDNNEHASQKILNQSYCFLGSLPIRQKIFGSEFASFPYLSFYGNAKEAYFDNTYYPTRCGWIVEKLNTTQDQFLRDGDEVRLKHVSSGKYLATTPLKDTHGTLTRTTNCEDAIFIIKKSSGYSEQ ID NO: 67 - CT601 fragment nucleotide sequenceGGTAAAGCACCGTCTTTGCAGGCTATTCTAGCCGAAGTCGAAGACACCTCCTCTCGTCTACACGCTCATCACAATGAGCTTGCTATGATCTCTGAACGCCTCGATGAGCAAGACACGAAACTACAGCAACTTTCGTCAACACAAGATCATAACCTACCTCGACAAGTTCAGCGACTAGAAACGGACCAAAAAGCTTTGGCAAAAACACTGGCGATTCTTTCGCAATCCGTCCAAGATATTCGGTCTTCTGTACAAAATAAATTACAAGAAATCCAACAAGAACAAAAAAAATTAGCACAAAATTTGCGAGCGCTTCGTAACTCTTTACAAGCTCTCGTTGATGGCTCTTCTCCAGAAAATTATATTGATTTCCTAACTGGTGAAACCCCGGAACATATTCATATTGTTAAACAAGGAGAGACCCTGAGCAAGATCGCGAGTAAATATAACATCCCCGTCGTAGAATTAAAAAAACTTAATAAACTAAATTCGGATACTATTTTTACAGATCAAAGAATTCGCCTTCCGAAAAAGAAASEQ ID NO: 68 - CT601 fragment protein sequenceGKAPSLQAILAEVEDTSSRLHAHHNELAMISERLDEQDTKLQQLSSTQDHNLPRQVQRLETDQKALAKTLAILSQSVQDIRSSVQNKLQEIQQEQKKLAQNLRALRNSLQALVDGSSPENYIDFLTGETPEHIHIVKQGETLSKIASKYNIPVVELKKLNKLNSDTIFTDQRIRLPKKKSEQ ID NO: 69 - CT279 fragment nucleotide sequenceGCACAAGTAATTTCTTCCGATAACACATTCCAAGTCTATGAAAAGGGAGATTGGCACCCAGCCCTATATAATACTAAAAAGCAGTTGCTAGAGATCTCCTCTACTCCTCCTAAAGTAACCGTGACAACTTTAAGCTCATATTTTCAAAACTTTGTTAGAGTCTTGCTTACAGATACACAAGGAAATCTTTCTTCATTCGAAGACCATAATCTCAATCTAGAAGAATTTTTATCTCAACCAACTCCTGTAATACATGGTCTTGCCCTTTATGTGGTCTACGCTATCCTACACAACGATGCAGCTTCCTCTAAATTATCTGCTTCCCAAGTAGCGAAAAATCCAACAGCTATAGAATCTATAGTTCTTCCTATAGAAGGTTTTGGTTTGTGGGGACCTATCTATGGATTCCTTGCTCTAGAAAAAGACGGGAATACTGTTCTTGGTACTTCTTGGTATCAACATGGCGAGACTCCTGGATTAGGAGCAAATATCGCTAACCCTCAATGGCAAAAAAATTTCAGAGGCAAAAAAGTATTTCTAGTCTCAGCTTCTGGAGAAACAGATTTTGCTAAGACAACCCTAGGACTGGAAGTTATAAAAGGATCTGTATCTGCAGCATTAGGAGACTCACCTAAAGCTGCTTCTTCCATCGACGGAATTTCAGGAGCTACTTTGACTTGTAATGGTGTTACCGAATCCTTCTCTCATTCTCTAGCTCCCTACCGCGCTTTGTTGACTTTCTTCGCCAACTCTAAACCTAGTGGAGAGTCTCATGACCAC SEQ ID NO: 70 - CT279 fragment protein sequenceAQVISSDNTFQVYEKGDWHPALYNTKKQLLEISSTPPKVTVTTLSSYFQNFVRVLLTDTQGNLSSFEDHNLNLEEFLSQPTPVIHGLALYVVYAILHNDAASSKLSASQVAKNPTAIESIVLPIEGFGLWGPIYGFLALEKDGNTVLGTSWYQHGETPGLGANIANPQWQKNFRGKKVFLVSASGETDFAKTTLGLEVIKGSVSAALGDSPKAASSIDGISGATLTCNGVTESFSHSLAPYRALLTFFANSKPSGESHDHSEQ ID NO: 71 - CT443 fragment nucleotide sequenceGGGGTGTTAGAGACCTCTATGGCAGAGTCTCTCTCTACAAACGTTATTAGCTTAGCTGACACCAAAGCGAAAGACAACACTTCTCATAAAAGCAAAAAAGCAAGAAAAAACCACAGCAAAGAGACTCCCGTAGACCGTAAAGAGGTTGCTCCGGTTCATGAGTCTAAAGCTACAGGACCTAAACAGGATTCTTGCTTTGGCAGAATGTATACAGTCAAAGTTAATGATGATCGCAATGTTGAAATCACACAAGCTGTTCCTGAATATGCTACGGTAGGATCTCCCTATCCTATTGAAATTACTGCTACAGGTAAAAGGGATTGTGTTGATGTTATCATTACTCAGCAATTACCATGTGAAGCAGAGTTCGTACGCAGTGATCCAGCGACAACTCCTACTGCTGATGGTAAGCTAGTTTGGAAAATTGACCGCTTAGGACAAGGCGAAAAGAGTAAAATTACTGTATGGGTAAAACCTCTTAAAGAAGGTTGCTGCTTTACAGCTGCAACAGTATGCGCTTGTCCAGAGATCCGTTCGGTTACAAAATGTGGACAACCTGCTATCTGTGTTAAACAAGAAGGCCCAGAGAATGCTTGTTTGCGTTGCCCAGTAGTTTACAAAATTAATATAGTGAACCAAGGAACAGCAACAGCTCGTAACGTTGTTGTTGAAAATCCTGTTCCAGATGGTTACGCTCATTCTTCTGGACAGCGTGTACTGACGTTTACTCTTGGAGATATGCAACCTGGAGAGCACAGAACAATTACTGTAGAGTTTTGTCCGCTTAAACGTGGTCGTGCTACCAATATAGCAACGGTTTCTTACTGTGGAGGACATAAAAATACAGCAAGCGTAACAACTGTGATCAACGAGCCTTGCGTACAAGTAAGTATTGCAGGAGCAGATTGGTCTTATGTTTGTAAGCCTGTAGAATATGTGATCTCCGTTTCCAATCCTGGAGATCTTGTGTTGCGAGATGTCGTCGTTGAAGACACTCTTTCTCCCGGAGTCACAGTTCTTGAAGCTGCAGGAGCTCAAATTTCTTGTAATAAAGTAGTTTGGACTGTGAAAGAACTGAATCCTGGAGAGTCTCTACAGTATAAAGTTCTAGTAAGAGCACAAACTCCTGGACAATTCACAAATAATGTTGTTGTGAAGAGCTGCTCTGACTGTGGTACTTGTACTTCTTGCGCAGAAGCGACAACTTACTGGAAAGGAGTTGCTGCTACTCATATGTGCGTAGTAGATACTTGTGACCCTGTTTGTGTAGGAGAAAATACTGTTTACCGTATTTGTGTCACCAACAGAGGTTCTGCAGAAGATACAAATGTTTCTTTAATGCTTAAATTCTCTAAAGAACTGCAACCTGTATCCTTCTCTGGACCAACTAAAGGAACGATTACAGGCAATACAGTAGTATTCGATTCGTTACCTAGATTAGGTTCTAAAGAAACTGTAGAGTTTTCTGTAACATTGAAAGCAGTATCAGCTGGAGATGCTCGTGGGGAAGCGATTCTTTCTTCCGATACATTGACTGTTCCAGTTTCTGATACAGAGAATACACACATCTATSEQ ID NO: 72 - CT443 fragment protein sequenceGVLETSMAESLSTNVISLADTKAKDNTSHKSKKARKNHSKETPVDRKEVAPVHESKATGPKQDSCFGRMYTVKVNDDRNVEITQAVPEYATVGSPYPIEITATGKRDCVDVIITQQLPCEAEFVRSDPATTPTADGKLVWKIDRLGQGEKSKITVWVKPLKEGCCFTAATVCACPEIRSVTKCGQPAICVKQEGPENACLRCPVVYKINIVNQGTATARNVVVENPVPDGYAHSSGQRVLTFTLGDMQPGEHRTITVEFCPLKRGRATNIATVSYCGGHKNTASVTTVINEPCVQVSIAGADWSYVCKPVEYVISVSNPGDLVLRDVVVEDTLSPGVTVLEAAGAQISCNKVVWTVKELNPGESLQYKVLVRAQTPGQFTNNVVVKSCSDCGTCTSCAEATTYWKGVAATHMCVVDTCDPVCVGENTVYRICVTNRGSAEDTNVSLMLKFSKELQPVSFSGPTKGTITGNTVVFDSLPRLGSKETVEFSVTLKAVSAGDARGEAILSSDTLTVPVSDTENTHIYSEQ ID NO: 73 - CT372 fragment nucleotide sequenceCAGGCTGCACACCATCACTATCACCGCTACACAGATAAACTGCACAGACAAAACCATAAAAAAGATCTCATCTCTCCCAAACCTACCGAACAAGAGGCGTGCAATACTTCTTCCCTTAGTAAGGAATTAATCCCTCTATCAGAACAAAGAGGCCTTTTATCCCCCATCTGTGACTTTATTTCGGAACGCCCTTGCTTACACGGAGTTTCTGTTAGAAATCTCAAGCAAGCGCTAAAAAATTCTGCAGGAACCCAAATTGCACTGGATTGGTCTATTCTCCCTCAATGGTTCAATCCTCGGGTCTCTCATGCCCCTAAGCTTTCTATCCGAGACTTTGGGTATAGCGCACACCAAACTGTTACCGAAGCCACTCCTCCTTGCTGGCAAAACTGCTTTAATCCATCTGCGGCCGTTACTATCTATGATTCCTCATATGGGAAAGGGGTCTTTCAAATATCCTATACCCTTGTCCGCTATTGGAGAGAGAATGCTGCGACTGCTGGCGATGCTATGATGCTCGCAGGGAGTATCAATGATTATCCCTCTCGTCAGAACATTTTCTCTCAGTTTACTTTCTCCCAAAACTTCCCAAATGAACGGGTGAGTCTGACAATTGGTCAGTACTCACTCTATGCAATAGACGGAACATTATACAATAACGATCAACAACTTGGATTCATTAGTTACGCATTATCACAAAATCCAACAGCAACTTATTCCTCTGGAAGTCTTGGAGCTTACCTACAAGTCGCTCCTACCGCAAGCACAAGTCTTCAAATAGGATTTCAAGACGCTTATAATATCTCCGGATCCTCTATCAAATGGAGTAACCTTACAAAAAATAGATACAATTTTCACGGTTTTGCTTCCTGGGCTCCCCGCTGTTGCTTAGGATCTGGCCAGTACTCCGTGCTTCTTTATGTGACTAGACAAGTTCCAGAACAGATGGAACAAACAATGGGATGGTCAGTCAATGCGAGTCAACACATATCTTCTAAACTGTATGTGTTTGGAAGATACAGCGGTGTTACAGGACATGTGTTCCCGATTAACCGCACGTATTCATTCGGTATGGCCTCTGCAAATTTATTTAACCGTAACCCACAAGATTTATTTGGAATTGCTTGCGCATTCAATAATGTACACCTCTCTGCTTCTCCAAATACTAAAAGAAAATACGAAACTGTAATCGAAGGGTTTGCAACTATCGGTTGCGGCCCCTATCTTTCTTTCGCTCCAGACTTCCAACTCTACCTCTACCCAGCTCTTCGTCCAAACAAACAATCTGCCCGTGTTTATAGCGTGCGAGCTAATTTAGCTATC SEQ ID NO: 74 - CT372 fragment protein sequenceQAAHHHYHRYTDKLHRQNHKKDLISPKPTEQEACNTSSLSKELIPLSEQRGLLSPICDFISERPCLHGVSVRNLKQALKNSAGTQIALDWSILPQWFNPRVSHAPKLSIRDFGYSAHQTVTEATPPCWQNCFNPSAAVTIYDSSYGKGVFQISYTLVRYWRENAATAGDAMMLAGSINDYPSRQNIFSQFTFSQNFPNERVSLTIGQYSLYAIDGTLYNNDQQLGFISYALSQNPTATYSSGSLGAYLQVAPTASTSLQIGFQDAYNISGSSIKWSNLTKNRYNFHGFASWAPRCCLGSGQYSVLLYVTRQVPEQMEQTMGWSVNASRHISSKLYVFGRYSGVTGHVFPINRTYSFGMASANLFNRNPQDLFGIACAFNNVHLSASPNTKRKYETVIEGFATIGCGPYLSFAPDFQLYLYPALRPNKQSARVYSVRANLAISEQ ID NO: 75 - CT456 fragment nucleotide sequenceACAAATTCAGCGGCTACATCTTCTATCCAAACGACTGGAGAGACTGTAGTAAACTATACGAATTCAGCCTCCGCCCCCAATGTAACTGTATCGACCTCCTCTTCTTCCACACAAGCCACAGCCACTTCGAATAAAACTTCCCAAGCCGTTGCTGGAAAAATCACTTCTCCAGATACTTCAGAAAGCTCAGAAACTAGCTCTACCTCATCAAGCGATCATATCCCTAGCGATTACGATGACGTTGGTAGCAATAGTGGAGATATTAGCAACAACTACGATGACGTAGGTAGTAACAACGGAGATATCAGTAGCAATTATGACGATGCTGCTGCTGATTACGAGCCGATAAGAACTACTGAAAATATTTATGAGAGTATTGGTGGCTCTAGAACAAGTGGCCCAGAAAATACAAGTGGTGGTGCAGCAGCAGCACTCAATTCTCTAAGAGGCTCCTCCTACAGCAATTATGACGATGCTGCTGCTGATTACGAGCCGATAAGAACTACTGAAAATATTTATGAGAGTATTGGTGGCTCTAGAACAAGTGGCCCAGAAAATACGAGTGGTGGTGCAGCAGCAGCACTCAATTCTCTAAGAGGCTCCTCCTACAGCAATTATGACGATGCTGCTGCTGATTACGAGCCGATAAGAACTACTGAAAATATTTATGAGAGTATTGGTGGCTCTAGAACAAGTGGCCCAGAAAATACGAGTGATGGTGCAGCAGCAGCAGCACTCAATTCTCTAAGAGGCTCCTCCTACACAACAGGGCCTCGTAACGAGGGTGTATTCGGCCCTGGACCGGAAGGACTACCAGACATGTCTCTTCCTTCATACGATCCTACAAATAAAACCTCGTTATTGACTTTCCTCTCCAACCCTCATGTAAAGTCGAAAATGCTTGAAAACTCGGGGCATTTCGTCTTCATTGATACAGATAGAAGTAGTTTCATTCTTGTTCCTAACGGAAATTGGGACCAAGTCTGTTCAATTAAAGTTCAAAATGGAAAGACCAAAGAAGATCTCGACATCAAAGACTTGGAAAACATGTGTGCAAAATTCTGTACAGGGTTTAGCAAATTCTCTGGTGACTGGGACAGTCTTGTAGAACCTATGGTGTCAGCCAAAGCTGGAGTGGCCAGCGGAGGCAATCTTCCCAATACAGTGATTATCAATAATAAATTCAAAACTTGCGTTGCTTATGGTCCTTGGAATAGCCAGGAAGCAAGTTCTGGTTATACACCTTCTGCTTGGAGACGTGGTCATCGAGTAGATTTTGGAGGAATTTTTGAGAAAGCCAACGACTTTAATAAAATCAACTGGGGAACTCAAGCCGGGCCTAGTAGCGAAGACGATGGCATTTCCTTCTCCAATGAAACTCCTGGAGCTGGTCCTGCAGCTGCTCCATCACCAACGCCATCCTCTATTCCTATCATCAATGTCAATGTCAATGTTGGCGGAACTAATGTGAATATTGGAGATACGAATGTCAACACGACTAACACCACACCAACAACTCAATCTACAGACGCCTCTACAGATACAAGCGATATCGATGACATAAATACCAACAACCAAACTGATGATATCAATACGACAGACAAAGACTCTGACGGAGCTGGTGGAGTCAATGGCGATATATCCGAAACAGAATCCTCTTCTGGAGATGATTCAGGAAGTGTCTCTTCCTCAGAATCAGACAAGAATGCCTCTGTCGGAAATGACGGACCTGCTATGAAAGATATCCTTTCTGCCGTGCGTAAACACCTAGACGTCGTTTACCCTGGCGAAAATGGCGGTTCTACAGAAGGGCCTCTCCCAGCTAACCAAACTCTCGGAGACGTAATCTCTGATGTAGAGAATAAAGGCTCCGCTCAGGATACAAAATTGTCAGGAAATACAGGAGCTGGGGATGACGATCCAACAACCACAGCTGCTGTAGGTAATGGAGCGGAAGAGATCACTCTTTCCGACACAGATTCTGGTATCGGAGATGATGTATCCGATACAGCGTCTTCATCTGGGGATGAATCCGGAGGAGTCTCCTCTCCCTCTTCAGAATCCAATAAAAATACTGCCGTTGGAAATGACGGACCTTCTGGACTAGATATCCTCGCTGCCGTACGTAAACATTTAGATAAGGTTTACCCTGGCGACAATGGTGGTTCTACAGAAGGGCCTCTCCAAGCTAACCAAACTCTTGGAGATATCGTCCAGGATATGGAAACAACAGGGACATCCCAAGAAACCGTTGTATCCCCATGGAAAGGAAGCACTTCTTCAACGGAATCAGCAGGAGGAAGTGGTAGCGTACAAACACTACTGCCTTCACCACCTCCAACCCCGTCAACTACAACATTAAGAACGGGCACAGGAGCTACCACCACATCCTTGATGATGGGAGGACCAATCAAAGCTGACATAATAACAACTGGTGGCGGAGGACGAATTCCTGGAGGAGGAACGTTAGAAAAGCTGCTCCCTCGTATACGTGCGCACTTAGACATATCCTTTGATGCGCAAGGCGATCTCGTAAGTACTGAAGAGCCTCAGCTTGGCTCGATTGTAAACAAATTCCGCCAAGAAACTGGTTCAAGAGGAATCTTAGCTTTCGTTGAGAGTGCTCCAGGCAAGCCGGGATCTGCACAGGTCTTAACGGGTACAGGGGGAGATAAAGGCAACCTATTCCAAGCAGCTGCCGCAGTCACCCAAGCCTTAGGAAATGTTGCAGGGAAAGTCAACCTTGCGATACAAGGCCAAAAACTATCATCCCTAGTCAATGACGACGGGAAGGGGTCTGTTGGAAGAGATTTATTCCAAGCAGCAGCCCAAACAACTCAAGTGCTAAGCGCACTGATTGATACCGTAGGA SEQ ID NO: 76 - CT456 fragment protein sequenceTNSAATSSIQTTGETVVNYTNSASAPNVIVSTSSSSTQATATSNKTSQAVAGKITSPDTSESSETSSTSSSDHIPSDYDDVGSNSGDISNNYDDVGSNNGDISSNYDDAAADYEPIRTTENIYESIGGSRTSGPENTSGGAAAALNSLRGSSYSNYDDAAADYEPIRTTENIYESIGGSRTSGPENTSGGAAAALNSLRGSSYSNYDDAAADYEPIRTTENIYESIGGSRTSGPENTSDGAAAAALNSLRGSSYTTGPRNEGVFGPGPEGLPDMSLPSYDPTNKTSLLTFLSNPHVKSKMLENSGHFVFIDTDRSSFILVPNGNWDQVCSIKVQNGKTKEDLDIKDLENMCAKFCTGFSKFSGDWDSLVEPMVSAKAGVASGGNLPNTVIINNKFKTCVAYGPWNSREASSGYTPSAWRRGHRVDFGGIFEKANDFNKINWGTQAGPSSEDDGISFSNETPGAGPAAAPSPTPSSIPIINVNVNVGGTNVNIGDTNVNTTNTTPTTQSTDASTDTSDIDDINTNNQTDDINTTDKDSDGAGGVNGDISETESSSGDDSGSVSSSESDKNASVGNDGPAMKDILSAVRKHLDVVYPGENGGSTEGPLPANQTLGDVISDVENKGSAQDTKLSGNTGAGDDDPTTTAAVGNGAEEITLSDTDSGIGDDVSDTASSSGDESGGVSSPSSESNKNTAVGNDGPSGLDILAAVRKHLDKVYPGDNGGSTEGPLQANQTLGDIVQDMETTGTSQETVVSPWKGSTSSTESAGGSGSVQTLLPSPPPTPSTTTLRTGTGATTTSLMMGGPIKADIITTGGGGRIPGGGTLEKLLPRIRAHLDISFDAQGDLVSTEEPQLGSIVNKFRQETGSRGILAFVESAPGKPGSAQVLTGIGGDKGNLFRAAAAVTQALGNVAGKVNLAIQGQKLSSLVNDDGKGSVGRDLFQAAAQTTQVLSALIDTVGSEQ ID NO: 77: CT381 fragment nucleotide sequenceTGTTTAAAAGAAGGGGGAGACTCCAATAGTGAAAAATTTATTGTAGGGACTAATGCAACCTACCCTCCTTTTGAGTTTGTTGATAAGCGAGGAGAGGTTGTAGGCTTCGATATAGACTTGGCTAGAGAGATTAGTAACAAGCTGGGGAAAACGCTGGACGTTCGGGAGTTTTCCTTTGATGCACTCATTCTAAACCTAAAACAGCATCGGATTGATGCGGTTATAACAGGGATGTCCATTACTCCTTCTAGATTGAAGGAAATTCTTATGATTCCCTATTATGGGGAGGAAATAAAACACTTGGTTTTAGTGTTTAAAGGAGAGAATAAGCATCCATTGCCACTCACTCAATATCGTTCTGTAGCTGTTCAAACAGGAACCTATCAAGAGGCCTATTTACAGTCTCTTTCTGAAGTTCATATTCGCTCTTTTGATAGCACTCTAGAAGTACTCATGGAAGTCATGCATGGTAAATCTCCCGTCGCTGTTTTAGAGCCATCTATCGCTCAAGTTGTCTTGAAAGATTTCCCGGCTCTTTCTACAGCAACCATAGATCTCCCTGAAGATCAGTGGGTTTTAGGATACGGGATTGGCGTTGCTTCAGATCGCCCAGCTTTAGCCTTGAAAATCGAGGCAGCTGTGCAAGAGATCCGAAAAGAAGGAGTGCTAGCAGAGTTGGAACAGAAGTGGGGTTTGAACAAC SEQ ID NO: 78: CT381 fragment protein sequenceCLKEGGDSNSEKFIVGTNATYPPFEFVDKRGEVVGFDIDLAREISNKLGKTLDVREFSFDALILNLKQHRIDAVITGMSITPSRLKEILMIPYYGEEIKHLVLVFKGENKHPLPLTQYRSVAVQTGTYQEAYLQSLSEVHIRSFDSTLEVLMEVMHGKSPVAVLEPSIAQVVLKDFPALSTATIDLPEDQWVLGYGIGVASDRPALALKIEAAVQEIRKEGVLAELEQKWGLNN SEQ ID NO: 79: CT043 fragment nucleotide sequenceTCCAGGCAGAATGCTGAGGAAAATCTAAAAAATTTTGCTAAAGAGCTTAAACTCCCCGACGTGGCCTTCGATCAGAATAATACGTGCATTTTGTTTGTTGATGGAGAGTTTTCTCTTCACCTGACCTACGAAGAACACTCTGATCGCCTTTATGTTTACGCACCTCTTCTTGACGGACTGCCAGACAATCCGCAAAGAAGGTTAGCTCTATATGAGAAGTTGTTAGAAGGCTCTATGCTCGGAGGCCAAATGGCTGGTGGAGGGGTAGGAGTCGCTACTAAGGAACAGTTGATCTTAATGCACTGCGTGTTAGACATGAAGTATGCAGAGACCAACCTACTCAAAGCTTTTGCACAGCTTTTTATTGAAACCGTTGTGAAATGGCGAACTGTTTGTTCTGATATCAGCGCTGGACGAGAACCCACTGTTGATACCATGCCACAAATGCCTCAAGGGGGTGGCGGAGGAATTCAACCTCCTCCAGCAGGAATCCGTGCASEQ ID NO: 80: CT043 fragment protein sequenceSRQNAEENLKNFAKELKLPDVAFDQNNTCILFVDGEFSLHLTYEEHSDRLYVYAPLLDGLPDNPQRRLALYEKLLEGSMLGGQMAGGGVGVATKEQLILMHCVLDMKYAETNLLKAFAQLFIETVVKWRTVCSDISAGREPTVDTMPRMPQGGGGGIQPPPAGIRA SEQ ID NO: 81: CT711 fragment nucleotide.seq Length: 2298TCAATACAACCTACATCCATTTCTTTAACTAAGAATATAACGGCAGCTTTAGCCGGAGAGCAGGTCGATGCTGCTGCAGTGTATATGCCGCAGGCTGTTTTTTTCTTTCAGCAACTGGATGAAAAAAGCAAGGGGCTGAAACAGGCTTTAGGATTGCTCGAAGAGGTTGATCTAGAAAAATTTATACCGTCTTTAGAAAAATCACCTACACCTATCACTACGGGAACAACGAGTAAAATTTCCGCTGATGGGATTGAGATTGTTGGAGAGCTTTCTTCAGAAACAATTTTGGCAGATCCTAATAAAGCTGCAGCTCAGGTTTTTGGAGAGGGGCTTGCAGATAGTTTTGATGATTGGCTCAGATTATCTGAAAATGGGGGGATTCAAGATCCTACAGCAATAGAAGAAGAGATTGTTACTAAGTATCAAACAGAACTCAATACTCTGCGCAATAAACTCAAGCAACAATCTTTAACAGACGATGAGTATACGAAGCTTTATGCTATTCCTCAAAACTTTGTTAAAGAGATAGAAAGCTTAAAGAATGAAAATAATGTGAGGTTAATTCCCAAAAGTAAAGTCACTAACTTTTGGCAGAATATCATGCTCACTTACAACTCGGTAACCTCGTTATCAGAACCTGTTACCGATGCGATGAATACGACTATGGCGGAGTACTCTCTTTATATTGAGAGAGCTACAGAGGCTGCCAAGTTGATACGGGAGATAACCAACACGATCAAAGACATTTTCAATCCAGTTTGGGATGTGCGTGAACAAACAGGAATTTTTGGGTTAAAAGGAGCTGAGTATAACGCTTTAGAAGGCAATATGATTCAAAGCTTGCTTAGCTTTGCGGGTCTATTCCGGCAGTTAATGAGTCGTACTGCAACAGTTGATGAGATAGGCGCACTTTATCCTAAAAATGATAAAAACGAAGACGTCATTCATACTGCTATTGATGATTATGTGAATTCTTTAGCTGATTTGAAAGCCAATGAACAGGTCAAACTCAACGGTCTGTTGAGTTTAGTATATGCTTATTATGCTAGTACTTTAGGTTTTGCTAAGAAGGATGTATTCAATAATGCACAAGCTTCTTTTACAGATTATACTAATTTTCTAAACCAAGAGATCCAATATTGGACGCCTAGAGAGACTTCAAGTTTTAATATCTCCAATCAAGCATTGCAAACCTTTAAAAATAAGCCTTCGGCTGATTATAACGGCGTATATCTTTTTGATAATAAAGGATTAGAGACTAATCTCTTTAATCCTACGTTCTTCTTTGATGTTGTGAGTCTCATGACAGCTGATCCTACGAAGACTATGTCTCGACAGGATTACAATAAGGTGATTACAGCCTCGGAATCCAGTATTCAGAAGATTAATCAGGCTATTACCGCTTGGGAACTAGCTATTGCAGAATGTGGGACTAAAAAAGCGAAGCTCGAACCATCCAGTTTAAATTATTTTAATGCTATGGTCGAAGCGAAGAAGACCTTCGTAGAGACCTCTCCAATACAGATGGTCTATTCATCTTTGATGTTGGATAAGTATCTTCCGAATCAGCAGTACATATTAGAGACATTAGGAAGTCAGATGACTTTCTCTAACAAGGCTGCTCGGTATTTAAATGATATCATTGCGTATGCAGTTAGCTTCCAAACAGCTGACGTCTATTATTCTTTAGGGATGTATCTTCGACAAATGAACCAGCAGGAATTTCCTGAGGTGATTTCTCGTGCTAACGATACTGTGAAAAAAGAGATAGATCGGAGTCGTGCGGATCTCTTTCACTGTAAAAAAGCTATCGAAAAGATTAAAGAATTAGTGACTTCTGTAAATGCGGATACTGAATTGACCTCATCTCAGCGTGCAGAGTTATTAGAGACGTTAGCTAGTTATGCTTTTGAATTTGAGAATCTCTATCACAACCTCTCTAATGTTTACGTCATGGTTTCTAAGGTACAGATTTCTGGCGTAAGCAAGCCTGATGAAGTGGATGAGGCTTTTACTGCTAAGATTGGATCGAAGGAATTCGATACTTGGATTCAGCAGCTTACAACATTTGAAAGTGCTGTGATTGAAGGTGGGCGTAATGGTGTGATGCCTGGGGGAGAGCAGCAGGTTTTACAGAGTTTAGAGAGCAAGCAGCAAGATTACACGTCGTTCAACCAGAATCAGCAATTAGCTCTACAAATGGAGTCCGCAGCGATTCAACAAGAGTGGACTATGGTAGCAGCAGCCTTAGCATTAATGAATCAGATTTTTGCTAAGTTGATCCGTAGATTTAAASEQ ID NO: 82: CT711 fragment protein sequence (AAC68306)SIQPTSISLTKNITAALAGEQVDAAAVYMPQAVFFFQQLDEKSKGLKQALGLLEEVDLEKFIPSLEKSPTPITTGTTSKISADGIEIVGELSSETILADPNKAAAQVFGEGLADSFDDWLRLSENGGIQDPTAIEEEIVTKYQTELNTLRNKLKQQSLTDDEYTKLYAIPQNFVKEIESLKNENNVRLIPKSKVTNFWQNIMLTYNSVTSLSEPVTDAMNTTMAEYSLYIERATEAAKLIREITNTIKDIFNPVWDVREQTGIFGLKGAEYNALEGNMIQSLLSFAGLFRQLMSRTATVDEIGALYPKNDKNEDVIHTAIDDYVNSLADLKANEQVKLNGLLSLVYAYYASTLGFAKKDVFNNAQASFTDYTNFLNQEIQYWTPRETSSFNISNQALQTFKNKPSADYNGVYLFDNKGLETNLFNPTFFFDVVSLMTADPTKTMSRQDYNKVITASESSIQKINQAITAWELAIAECGTKKAKLEPSSLNYFNAMVEAKKTFVETSPIQMVYSSLMLDKYLPNQQYILETLGSQMTFSNKAARYLNDIIAYAVSFQTADVYYSLGMYLRQMNQQEFPEVISRANDTVKKEIDRSRADLFHCKKAIEKIKELVTSVNADTELTSSQRAELLETLASYAFEFENLYHNLSNVYVMVSKVQISGVSKPDEVDEAFTAKIGSKEFDTWIQQLTTFESAVIEGGRNGVMPGGEQQVLQSLESKQQDYTSFNQNQQLALQMESAAIQQEWTMVAAALALMNQIFAKLIRRFKSEQ ID NO: 83: CT114 fragment nucleotide sequence - Length: 1296GATCCTTTGAGTGCAAAACAGTTAATGTATCTGTTTCCTCAGCTCTCAGAAGAGGATGTATCTGTTTTTGCTCGATGCATTTTGTCTTCAAAGCGTCCAGAATACCTCTTTTCAAAATCGGAGGAAGAGCTCTTTGCAAAATTGATTTTGCCAAGGGTTTCTCTAGGTGTTCATCGGGACGATGATTTAGCGAGAGTGTTGGTGTTAGCGGAGCCTTCTGCAGAAGAGCAGAAGGCTCGATACTATTCATTGTATCTGGATGTTTTAGCTTTGCGTGCATACGTTGAAAGAGAGCGTTTGGCGAGTGCTGCACACGGAGATCCTGAGCGGATAGATTTGGCAACCATAGAAGCTATTAATACCATCCTTTTTCAGGAAGAAGGATGGAGGTATCCTTCAAAACAAGAGATGTTTGAAAACAGGTTTTCTGAGTTAGCTGCTGTTACAGATAGTAAGTTTGGAGTTTGCTTGGGAACTGTAGTGCTTTATCAAGCTGTCGCCCAGCGGCTTGATTTGTCTCTGGACCCTGTCACCCCTCCTGGACATATTTACTTACGCTATAAGGACAAGGTGAATATTGAAACCACTTCTGGAGGAAGGCATCTTCCTACTGAAAGGTATTGTGAATGCATAAAAGAGTCGCAGTTAAAGGTGCGTTCGCAGATGGAGCTTATAGGGTTAACTTTTATGAATAGAGGAGCTTTCTTTTTGCAAAAAGGAGAGTTTCTTCAGGCGTCCTTAGCTTATGAGCAAGCTCAATCATATTTATCAGACGAGCAGATTTCTGATTTGTTAGGGATTACTTATGTTCTTTTAGGAAAGAAGGCGGCGGGAGAGGCTCTTTTAAAGAAATCTGCAGAAAAGACTCGGCGAGGGTCATCTATCTATGACTATTTCCAAGGATATATTTCCCCCGAAATCCTAGGGGTGTTGTTTGCCGATTCAGGGGTGACCTATCAAGAAACTTTGGAGTATCGAAAAAAACTAGTGATGCTTTCCAAGAAGTATCCAAAAAGTGGATCTCTTAGGTTGAGGTTGGCGACAACAGCATTGGAGCTAGGGCTGGTCAAGGAGGGGGTGCAGTTGTTAGAAGAGAGTGTTAAGGATGCCCCAGAGGACCTCTCTTTACGTCTGCAGTTTTGTAAAATTCTTTGCAATCGACATGATTATGTCCGAGCAAAATATCATTTTGATCAAGCGCAAGCTCTTCTCATTAAAGAAGGGTTGTTTTCCGAAAAAACTTCCTATACTCTCTTAAAAACTATCGGGAAAAAGCTATCTCTTTTTGCTCCGAGTSEQ ID NO: 84: CT114 fragment protein sequence (AAC67705)DPLSAKQLMYLFPQLSEEDVSVFARCILSSKRPEYLFSKSEEELFAKLILPRVSLGVHRDDDLARVLVLAEPSAEEQKARYYSLYLDVLALRAYVERERLASAAHGDPERIDLATIEAINTILFQEEGWRYPSKQEMFENRFSELAAVTDSKFGVCLGTVVLYQAVAQRLDLSLDPVTPPGHIYLRYKDKVNIETTSGGRHLPTERYCECIKESQLKVRSQMELIGLTFMNRGAFFLQKGEFLQASLAYEQAQSYLSDEQISDLLGITYVLLGKKAAGEALLKKSAEKTRRGSSIYDYFQGYISPEILGVLFADSGVTYQETLEYRKKLVMLSKKYPKSGSLRLRLATTALELGLVKEGVQLLEESVKDAPEDLSLRLQFCKILCNRHDYVRAKYHFDQAQALLIKEGLFSEKTSYTLLKTIGKKLSLFAPSSEQ ID NO: 85: CT480 fragment nucleotide sequenceTCTTCAGATCTACTTGAAAAAGATGTGAAATCGATCAAAAGAGAACTCAAGGCTTTACATGAAGATGTTCTTGAGTTAGTCCGGATCTCGCATCAGCAAAAAAATTGGGTCCAGTCTACAGATTTTTCTGTTTCTCCAGAGATCAGTGTATTGAAGGATTGCGGAGATCCTGCGTTCCCTAATTTATTATGCGAAGACCCTTATGTTGAAAAAGTGGTCCCTTCGTTGTTAAAGGAAGGTTTTGTTCCGAAAGGTATTTTGCGTACAGCTCAAGTAGGAAGGCCTGATAACCTAAGTCCGTTTAATGGCTTTGTTAATATCGTTCGATTTTATGAATTGTGCGTTCCTAATTTGGCTGTTGAGCATGTTGGTAAATACGAGGAGTTTGCGCCTAGTTTAGCCTTAAAGATAGAAGAGCATTATGTAGAGGATGGGTCTGGGGATAAAGAATTTCATATTTATTTGCGTCCTAATATGTTTTGGGAGCCGATAGATCCTACGCTGTTCCCTAAAAATATAACTTTAGCAGACAGCTTCTTAAGACCACATCCTGTCACCGCTCATGATGTGAAGTTCTATTACGATGTAGTCATGAATCCCTATGTTGCAGAAATGCGTGCAGTGGCTATGAGATCTTATTTTGAGGATATGGTTTCGGTTCGGGTAGAAAACGATTTGAAATTAATCGTTCGTTGGAGAGCTCATACTGTACGTAATGAACAGGGAGAGGAAGAGAAAAAAGTGCTCTATTCTGCTTTCGCGAATACATTGGCACTCCAACCGTTACCTTGTTTCGTGTATCAGCATTTCGCAAATGGAGAGAAGATCGTTCCAGAAGATTCTGATCCCGATACGTATCGCAAAGATTCGGTATGGGCGCAAAACTTTTCTTCACATTGGGCGTATAATTACATAGTGAGCTGTGGAGCATTCCGATTTGCAGGGATGGATGATGAGAAAATTACTTTAGTTCGTAATCCTAATTATCATAATCCGTTTGCGGCTCTTGTGGAGAAGCGCTATATCTATATGAAAGATAGTACAGATTCTCTCTTCCAAGATTTCAAAGCTGGGAAGGTGGATATTGCGTATTTCCCTCCTAACCATGTCGATAATCTAGCGAGCTTCATGCAAACCTCTGCTTATAAGGAACAAGCTGCTAGAGGAGAGGCAATTTTAGAAAAAAATTCATCAGACCGGTCCTATTCTTACATCGGATGGAATTGTCTTTCTCTTTTCTTTAACAATCGTTCGGTACGACAAGCCATGAATATGTTGATCGATCGGGATCGCATTATTGAGCAGTGCTTGGATGGTCGTGGAGTCTCTGTGAGTGGGCCTTTTTCTCTCTGCTCTCCATCATACAACAGAGATGTAGAGGGATGGCAATACTCTCCGGAAGAGGCCGCACGTAAATTAGAGGAAGAGGGCTGGATCGATGCTGATGGAGATGGTATTCGTGAGAAAGTAATCGATGGAGTTGTAGTGCCTTTCCGTTTCCGGTTATGCTACTATGTGAAAAGTGTAACAGCACGAACGATTGCCGAATATGTAGCTACGGTATGTAAAGAGGTGGGTATCGAGTGTTGCTTACTCGGGTTAGATATGGCGGATTATTCACAAGCCCTCGAGGAGAAAAATTTCGATGCTATTCTTTCCGGATGGTGTTTAGGAACCCCTCCAGAAGATCCTCGTGCTCTATGGCATTCGGAAGGAGCTTTGGAGAAAGGATCTGCCAATGCTGTTGGATTTTGTAATGAGGAAGCAGACCGTATCATCGAACAGCTCAGTTACGAGTATGATTCTAATAAGCGCCAAGCCTTGTATCACCGTTTTCACGAGGTGATTCATGAGGAATCTCCTTACGCGTTTCTCTATTCAAGACAGTACTCCCTTGTCTATAAGGAGTTTGTAAAAAATATTTTTGTGCCAACAGAACATCAGGATTTGATTCCTGGAGCTCAAGATGAGACAGTGAATTTATCCATGTTGTGGGTAGATAAAGAGGAGGGTCGATGCTCCGCTATATCTSEQ ID NO: 86: CT480/oppA_4 fragment protein sequence (AAC68080)SSDLLEKDVKSIKRELKALHEDVLELVRISHQQKNWVQSTDFSVSPEISVLKDCGDPAFPNLLCEDPYVEKVVPSLLKEGFVPKGILRTAQVGRPDNLSPFNGFVNIVRFYELCVPNLAVEHVGKYEEFAPSLALKIEEHYVEDGSGDKEFHIYLRPNMFWEPIDPTLFPKNITLADSFLRPHPVTAHDVKFYYDVVMNPYVAEMRAVAMRSYFEDMVSVRVENDLKLIVRWRAHTVRNEQGEEEKKVLYSAFANTLALQPLPCFVYQHFANGEKIVPEDSDPDTYRKDSVWAQNFSSHWAYNYIVSCGAFRFAGMDDEKITLVRNPNYHNPFAALVEKRYIYMKDSTDSLFQDFKAGKVDIAYFPPNHVDNLASFMQTSAYKEQAARGEAILEKNSSDRSYSYIGWNCLSLFFNNRSVRQAMNMLIDRDRIIEQCLDGRGVSVSGPFSLCSPSYNRDVEGWQYSPEEAARKLEEEGWIDADGDGIREKVIDGVVVPFRFRLCYYVKSVTARTIAEYVATVCKEVGIECCLLGLDMADYSQALEEKNFDAILSGWCLGTPPEDPRALWHSEGALEKGSANAVGFCNEEADRIIEQLSYEYDSNKRQALYHRFHEVIHEESPYAFLYSRQYSLVYKEFVKNIFVPTEHQDLIPGAQDETVNLSMLWVDKEEGRCSAISSEQ ID NO: 87: CT089 fragment nucleotide.sequence - Length: 1194GCTGCAGCTACTCAAGATGCACAAGAGGTTATCGGCTCTCAGGAAGCTTCTGAGGCAAGTATGCTCAAAGGATGTGAGGATCTCATAAATCCTGCAGCTGCAACCCGAATCAAAAAAAAAGGAGAGAAGTTTGAATCATTAGAAGCTCGTCGCAAACCAACAGCGGATAAAGCAGAAAAGAAATCCGAGAGCACAGAGGAAAAAGGCGATACTCCTCTTGAAGATCGTTTCACAGAAGATCTTTCCGAAGTCTCCGGAGAAGATTTTCGAGGATTGAAAAATTCGTTCGATGATGATTCTTCTCCTGACGAAATTCTCGATGCGCTCACAAGTAAATTTTCTGATCCCACAATAAAGGATCTAGCTCTTGATTATCTAATTCAAACAGCTCCCTCTGATGGGAAACTTAAGTCCACTCTCATTCAGGCAAAGCATCAACTGATGAGCCAGAATCCTCAGGCGATTGTTGGAGGACGCAATGTTCTGTTAGCTTCAGAAACCTTTGCTTCCAGAGCAAATACATCTCCTTCATCGCTTCGCTCCTTATATTTCCAAGTAACCTCATCCCCCTCTAATTGCGCTAATTTACATCAAATGCTTGCTTCTTACTTGCCATCAGAGAAAACCGCTGTTATGGAGTTTCTAGTAAATGGCATGGTAGCAGATTTAAAATCGGAGGGCCCTTCCATTCCTCCTGCAAAATTGCAAGTATATATGACGGAACTAAGCAATCTCCAAGCCTTACACTCTGTAAATAGCTTTTTTGATAGAAATATTGGGAACTTGGAAAATAGCTTAAAGCATGAAGGACATGCCCCTATTCCATCCTTAACGACAGGAAATTTAACTAAAACCTTCTTACAATTAGTAGAAGATAAATTCCCTTCCTCTTCCAAAGCTCAAAAGGCATTAAATGAACTGGTAGGCCCAGATACTGGTCCTCAAACTGAAGTTTTAAACTTATTCTTCCGCGCTCTTAATGGCTGTTCGCCTAGAATATTCTCTGGAGCTGAAAAAAAACAGCAGCTGGCATCGGTTATCACAAATACGCTAGATGCGATAAATGCGGATAATGAGGATTATCCTAAACCAGGTGACTTCCCACGATCTTCCTTCTCTAGTACGCCTCCTCATGCTCCAGTACCTCAATCTGAGATTCCAACGTCACCTACCTCAACACAGCCTCCATCACCCSEQ ID NO: 88: CT089/lcrE fragment protein sequence (AAC67680)AAATQDAQEVIGSQEASEASMLKGCEDLINPAAATRIKKKGEKFESLEARRKPTADKAEKKSESTEEKGDTPLEDRFTEDLSEVSGEDFRGLKNSFDDDSSPDEILDALTSKFSDPTIKDLALDYLIQTAPSDGKLKSTLIQAKHQLMSQNPQAIVGGRNVLLASETFASRANTSPSSLRSLYFQVTSSPSNCANLHQMLASYLPSEKTAVMEFLVNGMVADLKSEGPSIPPAKLQVYMTELSNLQALHSVNSFFDRNIGNLENSLKHEGHAPIPSLTTGNLTKTFLQLVEDKFPSSSKAQKALNELVGPDTGPQTEVLNLFFRALNGCSPRIFSGAEKKQQLASVITNTLDAINADNEDYPKPGDFPRSSFSSTPPHAPVPQSEIPTSPTSTQPPSPSEQ ID NO: 89: CT734 fragment nucleotide sequence - Length: 591TGTTGCGCCAACTCTTATGGATCGACTCTTGCAAAAAATACAGCCGAGATAAAAGAAGAATCTGTTACACTTCGCGAGAAGCCGGATGCCGGCTGTAAAAAGAAATCTTCTTGTTACTTGAGAAAATTTTTCTCGCGCAAGAAACCTAAAGAGAAGACAGAGCCTGTGTTGCCGAACTTTAAGTCTTACGCAGATCCAATGACAGATTCCGAAAGAAAAGACCTTTCTTTCGTAGTATCTGCTGCTGCTGATAAGTCTTCTATTGCTTTGGCTATGGCTCAGGGGGAAATTAAAGGCGCATTATCGCGTATTAGAGAGATCCATCCTCTTGCATTGTTACAAGCTCTTGCAGAAGATCCTGCTTTAATTGCTGGAATGAAAAAGATGCAAGGACGGGATTGGGTCTGGAATATCTTTATCACAGAATTAAGCAAAGTTTTTTCTCAAGCAGCATCTTTAGGGGCTTTCAGCGTTGCAGACGTTGCCGCGTTCGCGTCGACCTTAGGATTAGACTCGGGGACCGTTACCTCAATTGTTGATGGGGAAAGGTGGGCTGAGCTGATCGATGTCGTGATTCAGAACCCTGCTATASEQ ID NO: 90: CT734 fragment protein sequence (AAC68329)CCANSYGSTLAKNTAEIKEESVTLREKPDAGCKKKSSCYLRKFFSRKKPKEKTEPVLPNFKSYADPMTDSERKDLSFVVSAAADKSSIALAMAQGEIKGALSRIREIHPLALLQALAEDPALIAGMKKMQGRDWVWNIFITELSKVFSQAASLGAFSVADVAAFASTLGLDSGTVTSIVDGERWAELIDVVIQNPAISEQ ID NO: 91: CT016 fragment nucleotide sequenceAAAGTTAAAATTAATGATCAGTTCATTTGTATTTCCCCATACATTTCTGCTCGATGGAATCAGATAGCTTTCATAGAGTCTTGTGATGGAGGGACGGAAGGGGGTATTACTTTGAAACTCCATTTAATTGATGGAGAGACAGTCTCTATACCTAATCTAGGACAAGCGATTGTTGATGAGGTGTTCCAAGAGCACTTGCTATATTTAGAGTCCACAGCTCCTCAGAAAAACAAGGAAGAGGAAAAAATTAGCTCTTTGTTAGGAGCTGTTCAACAAATGGCTAAAGGATGCGAAGTACAGGTTTTTTCTCAAAAGGGCTTGGTTTCTATGTTACTAGGAGGAGCTGGTTCGATTAATGTGTTGTTGCAACATTCTCCAGAACATAAGGATCATCCTGATCTTCCTACCGATTTACTGGAGAGGATAGCGCAAATGATGCGTTCATTATCTATAGGACCAACTTCTATTTTAGCTAAGCCAGAGCCTCATTGCAACTGTTTGCATTGTCAAATTGGACGAGCTACAGTGGAAGAAGAGGATGCCGGAGTATCGGATGAGGATCTTACTTTTCGTTCATGGGATATCTCTCAAAGTGGAGAAAAGATGTACACTGTTACAGATCCTTTGAATCCAGAAGAGCAGTTTAATGTGTATTTAGGAACGCCGATTGGATGCACATGTGGGCAGCCATACTGTGAACACGTGAAAGCTGTTCTTTATACTSEQ ID NO: 92: CT016 fragment protein sequence (AAC67606)KVKINDQFICISPYISARWNQIAFIESCDGGTEGGITLKLHLIDGETVSIPNLGQAIVDEVFQEHLLYLESTAPQKNKEEEKISSLLGAVQQMAKGCEVQVFSQKGLVSMLLGGAGSINVLLQHSPEHKDHPDLPTDLLERIAQMMRSLSIGPTSILAKPEPHCNCLHCQIGRATVEEEDAGVSDEDLTFRSWDISQSGEKMYTVTDPLNPEEQFNVYLGTPIGCTCGQPYCEHVKAVLYT SEQ ID NO: 93: CM homolog of CT279 =TC_0551 fragment nucleotide sequenceGCATCCAAGTCTCGTCATTATCTTAACCAGCCTTGGTACATTATCTTATTCATCTTTGTTCTTAGTCTGGTTGCTGGTACCCTTCTTTCTTCAGTTTCCTATGTTCTATCTCCAATCCAAAAACAAGCTGCAGAATTTGATCGTAATCAGCAAATGTTGATGGCCGCACAAATTATTTCCTATGACAATAAATTCCAAATATATGCTGAAGGGGATTGGCAACCTGCTGTCTATAATACAAAAAAACAGATACTAGAAAAAAGCTCTTCCACTCCACCACAAGTGACTGTGGCGACTCTATGCTCTTATTTTCAAAATTTTGTTAGAGTTTTGCTTACAGACTCCCAAGGGAATCTTTCTTCTTTTGAAGATCACAATCTTAACCTAGAAGAGTTCTTATCCCACCCCACATCTTCAGTACAAGATCACTCTCTGCATGTAATTTATGCTATTCTAGCAAACGATGAATCCTCTAAAAAGTTATCATCCTCCCAAGTAGCAAAAAATCCGGTATCCATAGAGTCTATTATTCTTCCTATAAAAGGATTTGGTTTATGGGGACCAATCTATGGATTTCTTGCTTTAGAAAAGGACGGTAATACGGTTCTAGGGACATGCTGGTATCAACATGGTGAGACTCCAGGATTAGGAGCAAATATAACTAATCCCCAATGGCAACAAAATTTCAGAGGAAAAAAAGTATTTCTCGCTTCCTCTTCCGGAGAAACCGATTTTGCTAAAACAACTCTAGGACTAGAAGTTATAAAAGGATCTGTTTCTGCATTATTAGGGGACTCTCCCAAAGCTAATTCCGCTGTTGATGGAATTTCAGGAGCTACACTGACCTGTAATGGAGTTACTGAAGCTTTTGCTAATTCGCTAGCTCCTTACCGCCCCTTATTGACTTTCTTCGCCAATCTTAACTCTAGTGGAGAATCTCATGACAACCAA SEQ ID NO: 94: CM homologue of CT279 =TC_0551 fragment protein sequenceASKSRHYLNQPWYIILFIFVLSLVAGTLLSSVSYVLSPIQKQAAEFDRNQQMLMAAQIISYDNKFQIYAEGDWQPAVYNTKKQILEKSSSTPPQVTVATLCSYFQNFVRVLLTDSQGNLSSFEDHNLNLEEFLSHPTSSVQDHSLHVIYAILANDESSKKLSSSQVAKNPVSIESIILPIKGFGLWGPIYGFLALEKDGNTVLGTCWYQHGETPGLGANITNPQWQQNFRGKKVFLASSSGETDFAKTTLGLEVIKGSVSALLGDSPKANSAVDGISGATLTCNGVTEAFANSLAPYRPLLTFFANLNSSGESHDNQ SEQ ID NO: 95: CM homologue of CT372 =TC_0651 fragment nucleotide sequenceAATGGAAAAGTTCTGTGTGAGGTTTCTGTGTCCTTCCGTTCGATTCTGCTGACGGCTCTGCTTTCACTTTCTTTTACAAACACTATGCAGGCTGCACACCATCATTATCACCGTTATGATGATAAACTACGCAGACAATACCATAAAAAGGACTTGCCCACTCAAGAGAATGTTCGGAAAGAGTTTTGTAATCCCTACTCTCATAGTAGTGATCCTATCCCTTTGTCACAACAACGAGGAGTCCTATCTCCTATCTGTGATTTAGTCTCAGAGTGCTCGTTTTTGAACGGGATTTCCGTTAGGAGTCTTAAACAAACACTGAAAAATTCTGCTGGGACTCAAGTTGCTTTAGACTGGTCTATCCTTCCTCAATGGTTCAATCCTAGATCCTCTTGGGCTCCTAAGCTCTCTATTCGAGATCTTGGATATGGTAAACCCCAGTCCCTTATTGAAGCAGATTCCCCTTGTTGTCAAACCTGCTTCAACCCATCTGCTGCTATTACGATTTACGATTCTTCATGTGGGAAGGGTGTTGTCCAAGTGTCATACACCCTTGTTCGTTATTGGAGAGAAACGGCTGCACTTGCAGGGCAAACTATGATGCTTGCAGGAAGTATTAATGATTATCCTGCTCGCCAAAACATATTCTCTCAACTTACATTTTCCCAAACTTTCCCTAATGAGAGAGTAAATCTAACTGTTGGTCAATACTCTCTTTACTCGATAGACGGAACGCTGTACAACAATGATCAGCAGCTAGGATTTATTAGTTATGCGTTGTCGCAAAATCCAACAGCGACTTATTCCTCTGGAAGCCTTGGCGCCTATCTACAAGTCGCTCCAACAGAAAGCACCTGTCTTCAAGTTGGGTTCCAAGATGCCTATAATATTTCAGGTTCCTCGATCAAATGGAATAATCTTACAAAAAATAAGTATAACTTCCATGGCTATGCATCTTGGGCTCCACACTGTTGCTTAGGACCTGGACAATACTCTGTTCTTCTTTATGTAACCAGAAAGGTTCCTGAGCAAATGATGCAGACAATGGGCTGGTCTGTGAATGCAAGTCAATACATCTCTTCTAAACTTTATGTATTTGGAAGATACAGCGGAGTCACAGGCCAATTGTCTCCTATTAACCGAACCTATTCATTTGGCTTAGTCTCTCCTAATTTATTGAACCGTAACCCACAAGACTTATTTGGAGTAGCTTGCGCATTCAATAATATACACGCCTCCGCCTTTCAAAATGCTCAAAGAAAATATGAAACTGTGATCGAGGGATTTGCAACTATTGGTTGCGGACCTTACATCTCCTTTGCTCCAGATTTCCAACTTTACCTCTATCCTGCTCTGCGTCCAAATAAACAAAGCGCCCGAGTCTATAGCGTTCGCGCAAACCTAGCTATT SEQ ID NO: 96: CM homologue of CT372 =TC_0651 fragment protein sequenceNGKVLCEVSVSFRSILLTALLSLSFTNTMQAAHHHYHRYDDKLRRQYHKKDLPTQENVRKEFCNPYSHSSDPIPLSQQRGVLSPICDLVSECSFLNGISVRSLKQTLKNSAGTQVALDWSILPQWFNPRSSWAPKLSIRDLGYGKPQSLIEADSPCCQTCFNPSAAITIYDSSCGKGVVQVSYTLVRYWRETAALAGQTMMLAGSINDYPARQNIFSQLTFSQTFPNERVNLTVGQYSLYSIDGTLYNNDQQLGFISYALSQNPTATYSSGSLGAYLQVAPTESTCLQVGFQDAYNISGSSIKWNNLTKNKYNFHGYASWAPHCCLGPGQYSVLLYVTRKVPEQMMQTMGWSVNASQYISSKLYVFGRYSGVTGQLSPINRTYSFGLVSPNLLNRNPQDLFGVACAFNNIHASAFQNAQRKYETVIEGFATIGCGPYISFAPDFQLYLYPALRPNKQSARVYSVRANLAI SEQ ID NO: 97: CM homologue of CT443 =TC_0727 fragment nucleotide sequenceAGCGGGGTGTTAGAGACCTCTATGGCAGAGTCTCTCTCTACCAACGTTATTAGCTTAGCTGACACCAAAGCGAAAGAGACCACTTCTCATCAAAAAGACAGAAAAGCAAGAAAAAATCATCAAAATAGGACTTCCGTAGTCCGTAAAGAGGTTACTGCAGTTCGTGATACTAAAGCTGTAGAGCCTAGACAGGATTCTTGCTTTGGCAAAATGTATACAGTCAAAGTTAATGATGATCGTAATGTAGAAATCGTGCAGTCCGTTCCTGAATATGCTACGGTAGGATCTCCATATCCTATTGAGATTACTGCTATAGGGAAAAGAGACTGTGTTGATGTAATCATTACACAGCAATTACCATGCGAAGCAGAGTTTGTTAGCAGTGATCCAGCTACTACTCCTACTGCTGATGGTAAGCTAGTTTGGAAAATTGATCGGTTAGGACAGGGCGAAAAGAGTAAAATTACTGTATGGGTAAAACCTCTTAAAGAAGGTTGCTGCTTTACAGCTGCAACGGTTTGTGCTTGTCCAGAGATCCGTTCGGTTACGAAATGTGGCCAGCCTGCTATCTGTGTTAAACAGGAAGGTCCAGAAAGCGCATGTTTGCGTTGCCCAGTAACTTATAGAATTAATGTAGTCAACCAAGGAACAGCAACAGCACGTAATGTTGTTGTGGAAAATCCTGTTCCAGATGGCTATGCTCATGCATCCGGACAGCGTGTATTGACATATACTCTTGGGGATATGCAACCTGGAGAACAGAGAACAATCACCGTGGAGTTTTGTCCGCTTAAACGTGGTCGAGTCACAAATATTGCTACAGTTTCTTACTGTGGTGGACACAAAAATACTGCTAGCGTAACAACAGTGATCAATGAGCCTTGCGTGCAAGTTAACATCGAGGGAGCAGATTGGTCTTATGTTTGTAAGCCTGTAGAATATGTTATCTCTGTTTCTAACCCTGGTGACTTAGTTTTACGAGACGTTGTAATTGAAGATACGCTTTCTCCTGGAATAACTGTTGTTGAAGCAGCTGGAGCTCAGATTTCTTGTAATAAATTGGTTTGGACTTTGAAGGAACTCAATCCTGGAGAGTCTTTACAATATAAGGTTCTAGTAAGAGCTCAAACTCCAGGGCAATTCACAAACAACGTTGTTGTGAAAAGTTGCTCTGATTGCGGTATTTGTACTTCTTGCGCAGAAGCAACAACTTACTGGAAAGGAGTTGCTGCTACTCATATGTGCGTAGTAGATACTTGTGATCCTATTTGCGTAGGAGAGAACACTGTTTATCGTATCTGTGTGACAAACAGAGGTTCTGCTGAAGATACAAATGTGTCCTTAATTTTGAAATTCTCTAAAGAATTACAACCTATATCTTTCTCTGGACCAACTAAAGGAACCATTACAGGAAACACGGTAGTGTTTGATTCGTTACCTAGATTAGGTTCTAAAGAAACTGTAGAGTTTTCTGTAACGTTGAAAGCAGTATCCGCTGGAGATGCTCGTGGGGAAGCTATTCTTTCTTCCGATACATTGACAGTTCCTGTATCTGATACGGAGAATACACATATCTATSEQ ID NO: 98: CM homologue of CT443 = TC_0727 fragment protein sequenceSGVLETSMAESLSTNVISLADTKAKETTSHQKDRKARKNHQNRTSVVRKEVTAVRDTKAVEPRQDSCFGKMYTVKVNDDRNVEIVQSVPEYATVGSPYPIEITAIGKRDCVDVIITQQLPCEAEFVSSDPATTPTADGKLVWKIDRLGQGEKSKITVWVKPLKEGCCFTAATVCACPEIRSVTKCGQPAICVKQEGPESACLRCPVTYRINVVNQGTATARNVVVENPVPDGYAHASGQRVLTYTLGDMQPGEQRTITVEFCPLKRGRVTNIATVSYCGGHKNTASVTTVINEPCVQVNIEGADWSYVCKPVEYVISVSNPGDLVLRDVVIEDTLSPGITVVEAAGAQISCNKLVWTLKELNPGESLQYKVLVRAQTPGQFTNNVVVKSCSDCGICTSCAEATTYWKGVAATHMCVVDTCDPICVGENTVYRICVTNRGSAEDTNVSLILKFSKELQPISFSGPTKGTITGNTVVFDSLPRLGSKETVEFSVTLKAVSAGDARGEAILSSDTLTVPVSDTENTHIYSEQ ID NO: 99: CM homologue of CT043 =TC_0313 fragment nucleotide sequenceTCCAGACAGAATGCTGAGGAAAATCTAAAAAATTTTGCTAAAGAGCTCAAGCTCCCCGACGTGGCCTTCGATCAGAATAATACGTGCATTTTGTTTGTTGATGGAGAGTTTTCTCTTCACCTGACCTACGAAGAGCACTCTGATCGCCTTTATGTTTACGCACCTCTCCTTGACGGACTCCCAGATAATCCGCAAAGAAAGTTGGCTCTGTATGAGAAATTGTTGGAAGGCTCTATGCTCGGAGGCCAAATGGCTGGTGGAGGAGTAGGAGTTGCTACTAAAGAACAGTTGATCCTAATGCATTGCGTGTTAGATATGAAATATGCAGAGACTAATCTATTGAAAGCTTTTGCACAGCTTTTCATTGAAACTGTTGTGAAATGGCGAACGGTCTGTTCTGATATCAGCGCTGGACGAGAACCTTCCGTTGACACTATGCCTCAAATGCCTCAAGGAGGCAGCGGAGGAATTCAACCTCCTCCAACAGGAATTCGTGCGSEQ ID NO: 100: CM homologue of CT043 =TC_0313 fragment protein sequenceSRQNAEENLKNFAKELKLPDVAFDQNNTCILFVDGEFSLHLTYEEHSDRLYVYAPLLDGLPDNPQRKLALYEKLLEGSMLGGQMAGGGVGVATKEQLILNHCVLDMKYAETNLLKAFAQLFIETVVKWRTVCSDISAGREPSVDTMPQMPQGGSGGIQPPPTGIRA SEQ ID NO: 101: CM homologue of CT601 =TC_0890 fragment nucleotide sequenceCTCGCTAATCGGTTATTTCTAATCACCCTTATAGGTTTTGGCTATTCTGCTTACGGTGCCAGCACAGGGAAATCACCTTCTTTACAGGTTATTTTAGCTGAAGTCGAGGATACATCTTCGCGCTTACAAGCTCATCAGAATGAGCTTGTTATGCTCTCGGAACGTTTAGATGAGCAAGACACAAAACTTCAACAACTCTCGTCAACTCAGGCCCGTAATCTTCCTCAACAAGTTCAACGGCTTGAGATTGATCTGAGAGCTCTGGCTAAAACAGCTGCTGTGCTCTCGCAATCTGTTCAGGATATCCGATCATCCGTGCAAAATAAATTACAAGAAATCCAACAAGAACAAAAAAATTTAGCTCAAAATTTACGAGCGCTTCGCAACTCCTTACAAGCACTAGTTGATGGCTCTTCCCCAGAAAATTATATTGATTTTTTGGCCGGGGAGACACCTGAACATATTCACGTTGTTAAACAAGGAGAAACCCTGAGTAAAATCGCTAGTAAGTACAATATCCCTGTCGCAGAATTGAAAAAACTTAATAAATTAAATTCCGATACTATTTTTACTGATCAAAGAATCCGACTTCCAAAAAAGAAASEQ ID NO: 102: CM homologue of CT601 =TC_0890 fragment protein sequenceLANRLFLITLIGFGYSAYGASTGKSPSLQVILAEVEDTSSRLQAHQNELVMLSERLDEQDTKLQQLSSTQARNLPQQVQRLEIDLRALAKTAAVLSQSVQDIRSSVQNKLQEIQQEQKNLAQNLRALRNSLQALVDGSSPENYIDFLAGETPEHIHVVKQGETLSKIASKYNIPVAELKKLNKLNSDTIFTDQRIRLPKKKSEQ ID NO: 103: CM homologue of CT456 =TC_0741 fragment nucleotide sequenceACGACTCCAATAAGTAATTCTCCATCTTCTATTCCAACTGTTACAGTATCAACTACTACAGCATCTTCTGGATCTCTCGGAACTTCTACTGTATCATCAACGACTACAAGTACTTCAGTCGCACAAACAGCAACAACAACATCTTCTGCTTCTACATCTATAATTCAGTCTAGTGGAGAAAACATCCAATCCACTACAGGTACCCCTTCTCCTATTACGTCTAGTGTTTCAACATCCGCTCCATCTCCTAAAGCCTCCGCCACTGCAAACAAAACTTCAAGCGCTGTTTCTGGGAAAATTACCTCACAAGAAACTTCTGAGGAATCCGAAACCCAAGCCACTACATCTGATGGAGAAGTTAGTAGTAATTACGATGATGTTGATACCCCGACCAATTCGTCCGATTCGACAGTTGATAGTGATTACCAAGATGTTGAGACTCAGTACAAAACAATTAGCAACAATGGTGAAAACACTTATGAAACAATCGGAAGTCATGGTGAGAAAAACACACACGTCCAGGAAAGCCATGCATCCGGAACAGGAAATCCCATAAATAATCAGCAAGAAGCTATTAGACAGCTCCGATCATCTACCTATACAACCAGCCCTCGTAATGAGAATATATTTAGTCCAGGACCGGAAGGTCTACCTAATATGTCTCTTCCTAGTTACAGCCCTACAGATAAAAGTTCTCTACTAGCTTTCCTATCTAATCCCAATACAAAAGCAAAAATGCTCGAACACTCCGGGCATTTAGTCTTTATAGACACAACTAGAAGTAGCTTTATCTTTGTTCCGAATGGAAATTGGGATCAAGTCTGTTCCATGAAGGTTCAGAATGGGAAAACTAAAGAAGACCTTGGCTTAAAGGACTTAGAAGATATGTGTGCAAAGTTTTGCACAGGATACAATAAATTCTCCTCTGATTGGGGAAATCGAGTTGACCCCTTGGTCTCTTCTAAGGCCGGGATAGAAAGTGGGGGGCACCTCCCAAGCTCAGTTATCATCAACAACAAATTTAGAACCTGTGTTGCCTATGGGCCGTGGAACCCCAAAGAAAACGGCCCCAATTATACTCCTTCAGCCTGGAGACGTGGGCATCGAGTAGATTTTGGAAAGATCTTTGATGGAACAGCGCCGTTTAATAAAATCAACTGGGGCTCTTCCCCTACCCCTGGTGATGACGGCATCTCCTTCTCTAATGAAACTATTGGGTCTGAACCATTCGCGACACCTCCCTCATCCCCATCGCAAACCCCCGTTATCAACGTCAATGTTAATGTCGGTGGAACCAATGTTAATATTGGGGATACAAACGTATCTAAAGGATCCGGCACACCAACATCTTCTCAATCTGTGGACATGTCTACAGATACTAGCGATTTAGATACCAGTGATATTGATACAAACAACCAAACTAACGGCGATATCAACACGAATGACAACTCCAATAATGTCGATGGAAGTTTATCTGACGTTGATTCAAGGGTGGAAGACGATGACGGTGTATCGGATACAGAGTCCACTAATGGCAATGACTCTGGTAAAACTACTTCCACAGAAGAAAATGGTGACCCAAGCGGACCAGACATCCTGGCTGCTGTACGTAAACACCTAGACACTGTCTATCCAGGAGAAAATGGCGGATCTACAGAAGGACCTCTCCCTGCTAATCAAAATCTGGGGAACGTTATCCATGATGTGGAGCAGAATGGATCTGCTAAAGAAACTATTATCACTCCAGGAGATACAGGGCCTACAGACTCAAGCTCCTCTGTAGATGCTGATGCAGACGTTGAAGATACTTCTGATACTGACTCTGGAATCGGAGACGACGACGGTGTATCGGATACAGAGTCCACTAATGGTAATAACTCTGGTAAAACTACTTCCACAGAAGAAAATGGTGACCCAAGCGGACCAGACATCCTGGCTGCTGTACGTAAACACCTAGACACTGTCTATCCAGGAGAAAATGGCGGATCTACAGAAGGACCTCTCCCTGCTAATCAAAATCTGGGGAACGTTATCCATGATGTAGAACAAAACGGAGCCGCTCAAGAAACTATTATCACTCCAGGAGATACGGAATCTACAGACACAAGCTCTAGTGTAAATGCTAATGCAGACTTAGAAGATGTTTCTGATGCTGATTCAGGATTCGGGGATGATGACGGTATATCGGATACAGAGTCCACTAATGGTAACGACTCTGGAAAAAATACTCCTGTAGGGGATGGTGGTACACCAAGCGGACCAGATATCCTAGCTGCTGTACGCAAACATCTAGACACTGTCTATCCAGGAGAAAATGGTGGATCTACAGAGAGACCTTTACCCGCTAATCAAAATTTAGGAGATATCATTCATGATGTAGAACAAAACGGAAGCGCTAAAGAAACTGTAGTATCGCCTTATCGAGGAGGAGGAGGAAATACATCTTCCCCAATTGGATTAGCCTCCCTGCTTCCAGCAACACCATCCACACCTTTGATGACAACACCTAGAACAAATGGGAAAGCTGCAGCTTCTTCTTTGATGATAAAAGGAGGAGAAACTCAAGCCAAGCTAGTTAAGAATGGCGGCAATATCCCTGGAGAAACCACATTAGCAGAATTACTCCCTCGTTTAAGAGGACACCTTGACAAAGTCTTTACTTCAGACGGGAAGTTTACAAATCTTAATGGACCTCAACTTGGAGCCATCATAGACCAATTCCGCAAAGAAACGGGTTCCGGAGGAATCATAGCTCATACAGATAGTGTTCCAGGAGAGAACGGAACAGCCTCTCCTCTCACAGGAAGTTCAGGGGAAAAAGTCTCTCTCTATGATGCAGCGAAAAACGTCACTCAAGCTTTAACAAGTGTTACGAACAAAGTAACCCTAGCAATGCAAGGACAAAAACTGGAAGGAATTATAAACAACAACAATACCCCCTCTTCTATTGGACAAAATCTTTTCGCAGCAGCGAGGGCAACGACACAATCCCTCAGTTCATTAATTGGAACCGTACAA SEQ ID NO: 104: CM homologue of CT456 =TC_0741 fragment protein sequenceTTPISNSPSSIPTVTVSTTTASSGSLGTSTVSSTTTSTSVAQTATTTSSASTSIIQSSGENIQSTTGTPSPITSSVSTSAPSPKASATANKTSSAVSGKITSQETSEESETQATTSDGEVSSNYDDVDTPTNSSDSTVDSDYGDVETQYKTISNNGENTYETIGSHGEKNTHVQESHASGTGNPINNQQEAIRQLRSSTYTTSPRNENIFSPGPEGLPNMSLPSYSPTDKSSLLAFLSNPNTKAKMLEHSGHLVFIDTTRSSFIFVPNGNWDQVCSMKVQNGKTKEDLGLKDLEDMCAKFCTGYNKFSSDWGNRVDPLVSSKAGIESGGHLPSSVIINNKFRTCVAYGPWNPKENGPNYTPSAERRGHRVDFGKIFDGTAPFNKINWGSSPTPGDDGISFSNETIGSEPFATPPSSPSQTPVINVNVNVGGTNVNIGDTNVSKGSGTPTSSQSVDMSTDTSDLDTSDIDTNNQTNGDINTNDNSNNVDGSLSDVDSRVEDDDGVSDTESTNGNDSGKTTSTEENGDPSGPDILAAVRKHLDTVYPGENGGSTEGPLPANRNLGNVIHDVEQNGSAKETIITPGDTGPTDSSSSVDADADVEDTSDTDSGIGDDDGVSDTESTNGNNSGKTTSTEENGDPSGPDILAAVRKHLDTVYPGENGGSTEGPLPANQNLGNVIHDVEQNGAAQETIITPGDTESTDTSSSVNANADLEDVSDADSGFGDDDGISDTESTNGNDSGKNTPVGDGGTPSGPDILAAVRKHLDTVYPGENGGSTERPLPANQNLGDIIHDVEQNGSAKETVVSPYRGGGGNTSSPIGLASLLPATPSTPLMTTPRTNGKAAASSLMIKGGETQAKLVKNGGNIPGETTLAELLPRLRGHLDKVFTSDGKFTNLNGPQLGAIIDQFRKETGSGGIIAHTDSVPGENGTASPLTGSSGEKVSLYDAAKNVTQALTSVTNKVTLAMQGQKLEGIINNNNTPSSIGQNLFAAARATTQSLSSLIGTVQ SEQ ID NO: 105: CM homologue of CT381 =TC_0660 fragment nucleotide sequenceTGTTCAAAAGAGAGCAAAGACTCTGTTAGTGAAAAATTTATTGTAGGAACTAACGCAACGTATCCTCCTTTTGAGTTTGTTGATGAAAGAGGTGAGACGGTTGGCTTTGATATTGATTTAGCTAGGGAGATTAGTAAAAAGCTAGGGAAAAAATTAGAAGTCCGAGAATTTGCTTTTGATGCACTCGTTCTCAATTTAAAACAGCATCGTATTGATGCAATTATGGCAGGGGTGTCCATTACGTCTTCTCGATTGAAAGAAATTTTGATGATTCCCTACTATGGCGAAGAAATAAAGAGTTTGGTTTTAGTGTTTAAGGATGGAGACTCAAAGTCTTTACCACTAGATCAGTATAATTCTGTTGCTGTTCAAACTGGCACGTACCAAGAGGAATATTTACAGTCTCTTCCAGGGGTGCGTATTCGCTCTTTTGATAGTACTTTAGAAGTGCTTATGGAAGTTTTGCATAGCAAGTCTCCTATAGCTGTTTTAGAACCGTCTATTGCGCAGGTCGTTTTAAAAGATTTTCCGACGCTCACTACTGAAACGATAGATCTTCCTGAAGATAAATGGGTTTTAGGGTATGGAATTGGAGTTGCTTCTGATCGACCATCTCTAGCTTCTGATATAGAAGCTGCTGTACAAGAGATCAAGAAAGAAGGAGTGTTAGCAGAGTTAGAGCAAAAATGGGGTTTGAACGGC SEQ ID NO: 106: CM homologue of CT381 =TC_0660 fragment protein sequenceCSKESKDSVSEKFIVGTNATYPPFEFVDERGETVGFDIDLAREISKKLGKKLEVREFAFDALVLNLKQHRIDAIMAGVSITSSRLKEILMIPYYGEEIKSLVLVFKDGDSKSLPLDQYNSVAVQTGTYQEEYLQSLPGVRIRSFDSTLEVLMEVLHSKSPIAVLEPSIAQVVLKDFPTLTTETIDLPEDKWVLGYGIGVASDRPSLASDIEAAVQEIKKEGVLAELEQKWGLNG SEQ ID NO: 107 - CT255 fragment nucleotide sequenceGAAGAAAAAGGCATCTTACAATTGGTTGAAATTTCGCGAGCAATGGCTTTACAGGGAGTTTGTCCTTGGACTAATTTACAGAGTGTGGAGTCTATGTTGCAGTATATAGCAGGGGAGTGTCAGGAGTTGGCTGATGCTGTACAAGAAAATAAAGCTTCGTTGGAAATCGCTTCGGAAGCCGGAGACGTACTTACTTTAGTATTGACCTTGTGTTTCTTGCTAGAAAGAGAAGGAAAGCTTAAAGCTGAAGAAGTATTTGTAGAAGCTTTGGCTAAGTTGCGTCGTCGATCTCCTCATGTTTTTGATCCTCATAATCAAATTTCTTTAGAACAGGCTGAAGAATACTGGGCTCGTATGAAACAGCAAGAAAAAATTTCTSEQ ID NO: 108 - CT255 fragment protein sequenceEEKGILQLVEISRAMALQGVCPWINLQSVESMLQYIAGECQELADAVQENKASLEIASEAGDVLTLVLTLCFLLEREGKLKAEEVFVEALAKLRRRSPHVFDPHNQISLEQAEEYWARMKVJEKISSEQ ID NO: 109 - CT341 fragment nucleotide sequenceGATTACTACACGATATTGGGTGTAGCGAAGACTGCTACTCCTGAAGAAATAAAGAAAGCTTACCGTAAGCTCGCTGTAAAGTACCATCCAGATAAGAATCCTGGGGATGCTGAAGCGGAGCGACGCTTTAAAGAAGTTTCTGAAGCCTATGAAGTATTAGGTGATGCGCAGAAGCGGGAGTCATATGATCGTTACGGCAAAGACGGTCCATTTGCTGGTGCTGGAGGATTCGGTGGCGCTGGCATGGGGAATATGGAAGACGCTTTGCGAACATTTATGGGAGCTTTTGGCGGCGATTTCGGTGGTAATGGAGGCGGTTTCTTTGAAGGGCTTTTTGGAGGACTTGGAGAAGCTTTCGGAATGCGTGGAGGCTCAGAAAGTTCTCGACAAGGAGCTAGTAAGAAGGTGCATATTACGCTGTCCTTCGAGGAGGCGGCAAAAGGTGTTGAAAAAGAACTTCTTGTTTCAGGCTATAAATCTTGTGATGCTTGTTCTGGTAGTGGAGCCAATACTGCTAAAGGTGTAAAAGTTTGTGATCGATGCAAGGGCTCTGGTCAGGTAGTGCAAAGCCGAGGCTTTTTCTCCATGGCTTCTACTTGCCCTGATTGTAGTGGTGAAGGTCGGGTTATCACAGATCCTTGTTCAGTTTGTCGTGGGCAGGGACGTATCAAGGATAAACGTAGCGTCCATGTTAATATCCCAGCTGGAGTCGATTCTGGGATGAGATTAAAGATGGAAGGCTATGGAGATGCTGGCCAAAATGGAGCGCCTGCAGGGGATCTGTATGTTTTTATTGATGTAGAGCCTCATCCTGTTTTCGAGCGCCATGGGGATGATTTAGTTTTAGAGCTTCCTATTGGATTTGTTGATGCGGCTTTAGGGATCAAGAAGGAAATCCCTACACTCTTAAAAGAAGGTACTTGCCGTTTGAGTATCCCAGAAGGGATTCAGAGCGGAACAGTTCTTAAAGTTAGAGGGCAGGGATTCCCTAATGTGCATGGGAAATCCAGAGGAGATCTTTTAGTAAGAGTATCTGTGGAGACTCCCCAGCACCTATCTAATGAACAAAAAGATTTATTGAGACAGTTTGCTGCTACGGAGAAGGCTGAAAATTTCCCTAAGAAACGGAGTTTCTTAGACAAAATCAAAGGTTTTTTTTCTGACTTTGCTGTA SEQ ID NO: 110 - CT341 fragment protein sequenceDYYTILGVAKTATPEEIKKAYRKLAVKYHPDKNPGDAEAERRFKEVSEAYEVLGDAQKRESYDRYGKDGPFAGAGGFGGAGMGNMEDALRTFMGAFGGDFGGNGGGFFEGLFGGLGEAFGMRGGSESSRQGASKKVHITLSFEEAAKGVEKELLVSGYKSCDACSGSGANTAKGVKVCDRCKGSGQVVQSRGFFSMASTCPDCSGEGRVITDPCSVCRGQGRIKDKRSVHVNIPAGVDSGMRLKMEGYGDAGQNGAPAGDLYVFIDVEPHPVFERHGDDLVLELPIGFVDAALGIKKEIPTLLKEGTCRLSIPEGIQSGTVLKVRGQGFPNVHGKSRGDLLVRVSVETPQHLSNEQKDLLRQFAATEKAENFPKKRSFLDKIKGFFSDFAV SEQ ID NO: 111 - CT716 fragment nucleotide sequenceAATAAAAAACTCCAAGATCTGTCTAAACTGCTCACTATTGAGCTTTTCAAGAAACGTACACGGTTGGAAACAGTAAAAAAAGCGCTCTCCACAATAGAACATCGCTTACAACAAATACAGGAGCACATCGCGAAAATTTCCTTAACAAGGCACAAACAATTCCTATGTCGGTCATATACCCATGAATATGACCAACATTTAGAACATTTACAAAGAGAGCAAACTTCTCTATATAAACAGCATCAGACCCTGAAAACGTCTTTGAAAGATGCTTATGGCGACATACAAAAACAACTAGACCAAAGAAAAATTATCGAAAAGATCCATGACAGTAAATATCCTATAAAGAGCGCGAATAACSEQ ID NO: 112 - CT716 fragment protein sequenceNKKLQDLSKLLTIELFKKRTRLETVKKALSTIEHRLQQIQEHIAKISLTRHKRFLCRSYTHEYDQHLEHLQREQTSLYKQHQTLKTSLKDAYGDIQKQLDQRKIIEKIHDSKYPIKSANNSEQ ID NO: 113 - CT745 fragment nucleotide sequenceGCGTGGTGGCTACACAAACGATTCCCTCATGTGCAGCTGTCTATTCTAGAAAAAGAGTCTCGATCTGGAGGGCTAATTGTCACAGAGAAACAACAAGGGTTTTCCCTCAATATGGGCCCTAAAGGTTTTGTTTTAGCTCATGATGGGCAACACACCCTTCACCTCATTCAGTCTTTAGGCCTAGCAGACGAGCTATTATATAGCTCTCCAGAGGCTAAAAACCGCTTTATCCACTATAATAATAAAACCCGAAAAGTCTCGCCTTGGACTATTTTCAAACAAAATCTCCCTCTCTCTTTTGCTAAGGATTTCTTTGCGCGTCCTTACAAACAAGACAGCTCCGTGGAAGCCTTCTTTAAAAGACACAGTTCTTCCAAGCTTAGAAGAAATCTTTTAAATCCCATTAGCATTGCTATTCGTGCAGGACATAGTCATATATTGTCTGCACAGATGGCTTACCCAGAATTAACACGAAGAGAAGCTCAAACAGGATCGTTGTTACGTAGTTATCTCAAAGATTTTCCTAAAGAGAAACGCACAGGCCCTTATTTAGCTACCTTGCGGTCTGGGATGGGAATGCTAACCCAGGCTTTGCATGATAAATTGCCTGCTACCTGGTATTTTTCTGCACCCGTCAGCAAAATCCGTCAGTTGGCGAATGGGAAAATTTCTCTTTCATCTCCTCAAGGAGAAATAACGGGAGATATGCTCATTTATGCTGGGTCCGTGCACGATCTCCCTTCCTGTCTAGAAGGGATCCCTGAAACCAAGCTTATCAAGCAAACGACTTCATCTTGGGATCTCTCTTGTGTATCTTTAGGATGGCATGCATCCTTCCCTATCCCTCATGGATATGGCATGCTTTTCGCTGATACGCCTCCCTTATTAGGGATCGTGTTTAATACGGAAGTGTTCCCTCAACCCGAGCGGCCTAATACAATAGTCTCTCTTCTTTTAGAAGGTCGATGGCACCAAGAAGAAGCGTATGCTTTCTCACTAGCAGCTATTTCTGAGTACCTGCAAATTTACACTCCTCCCCAAGCTTTCTCACTATTCTCTCCTCGAGAGGGACTTCCCCAACACCATGTTGGATTTATCCAATCCCGCCAACGCCTTCTATCTAAACTTCCTCACAATATAAAAATTGTAGGGCAGAATTTTGCAGGTCCAGGTCTCAACCGCGCTACAGCGTCTGCTTATAAAGCTATAGCTTCTTTACTATCASEQ ID NO: 114 - CT745 fragment protein sequenceAWWLHKRFPHVQLSILEKESRSGGLIVTEKQQGFSLNMGPKGFVLAHDGQHTLHLIQSLGLADELLYSSPEAKNRFIHYNNKTRKVSPWTIFKQNLPLSFAKDFFARPYKQDSSVEAFFKRHSSSKLRRNLLNPISIAIRAGHSHILSAQMAYPELTRREAQTGSLLRSYLKDFPKEKRTGPYLATLRSGMGMLTQALHDKLPATWYFSAPVSKIRQLANGKISLSSPQGEITGDMLIYAGSVHDLPSCLEGIPETKLIKQTTSSWDLSCVSLGWHASFPIPHGYGMLFADTPPLLGIVFNTEVFPQPERPNTIVSLLLEGRWHQEEAYAFSLAAISEYLQIYTPPQAFSLFSPREGLPQHHVGFIQSRQRLLSKLPHNIKIVGQNFAGPGLNRATASAYKAIASLLSSEQ ID NO: 115 - CT387 fragment nucleotide sequenceACGCTCTTTCATTCTCATCATGATGCCGTCTCTCCAGACAGCTACCTATGTTCTTCCCTTCAGTTAGTTGGTACTGGCGTATACGAAGGAGAAATCGAGATTCAAAATATCCCCTCTTATTTCCTTGGATTCCAATTACCCTCTCATTGCATACACCTTAATTTAAAGAGCTCTCTAGCTCAATTAGGAATAGATGCCTCCCTTCTTCACTGCGAATTGAGCAAAAATCAACATCGAGCACATATACATGCTCAATTTACCGGTCATGGCCCCATTGCTGAATCTATGCTAGCCCTTCTCCAACCAGGAGATCGTGTAGCAAAACTATTTGCTGCAGACGATCGCAGACTGGTCCGATCTCCAGATTACCTCGAAAGCATGCTGAAAAATACAGATAAAGCTGGCCATCCTTTGCTCTGTTTTGGGAAAAAATTAGAACACTTGATTTCTTTTGATGTGGTAGATGATCGCCTTGTCGTCTCCCTTCCTACCCTGCCGGGAGTTGTTCGTTATGATTCGGATATTTATGGACTCCTTCCTCTTATTCAAAAATCACTCAGTAATCCCAAACTCAGCATTCGTCACTTTTTAGCTCTGTACCAACAGATTGTGGAAGGGCAACATGTCTCTTGCGGAAACCATATTCTTCTGATCAAAACAGAACCGCTGCACATCCGCACTGTATTTGCTCGCGTGGTAAATCAACTCCTCCCTCAAGGTCTCTCCCACACTTCTGCCAATATTTTGGAACCAACCACTCGAGAATCCGGGGATATCTTTGAATTTTTTGGGAACCCTTCTGCACAGATAGAAAGAATTCCTTTAGAATTTTTCACTATCGAACCCTATAAAGAACATTCTTACTTCTGTAATCGGGATTTATTACAAACCATCTTACAATCAGAAAGCGAAATCAAAAAAATATTCGAAACAGCGCCCAAAGAACCTGTCAAAGCTGCCACCTATTTATCAAAAGGCAGTGAAATCTCTTCCCTGCACACAGACTCTTGGCTCACAGGATCCGCAGCTGCCTATCAATATAGTGAGCAAGCAGATAAAAACGAGTACACTCATGCTCAACCTTGCTATCCTTTCTTAGAAGCAATGGAAATGGGCCTGATCAATAGCGAAGGAGCCTTACTCACTCGTTATTTCCCTTCAGCTAGCTTAAAAGGAATGTTGATTTCCTACCATGTGCGCCACTATCTCAAACAAATCTACTTTCAAGTTCCCTCTTATACACATGGAAACTATTTCTCTCATAATGACAGAGGTTTGCTATTAGATCTGCAGCAAGCAGATATTGATGTTTTCTGGGCAGATGAAGAAAGCGGCCGTGTGTTGCAATATACAAAACGACGCGATAAGAATAGCGGTATGTTCGTGATCAAAAATCGTGTTGAAGAGTTTCGATCAGCTTATTTTATTGCTATTTATGGCTCTCGTCTCCTTGAGAATAATTTCTCTGCTCAGCTCCATACCCTCCTAGCGGGCTTACAGCAAGCAGCACATACTCTCGGCATTCCTGGATTCTCAAAGCCTACCCCACTTGCAGTCATCACCGGAGGCGGCACTGGAGTTATGGCCACAGGAAATCGTGTAGCTAAAGAACTAGGAATCCTATCTTGTGGAACCGTTCTTGATTTAGAAGCTTCTCCAGCACAAATCGACCAACCTACCAATGAATTCTTAGATGCTAAAATGACATACCGCCTACCTCAACTTATAGAAAGGCAAGAACACTTTTATGCAGACCTTCCTATCCTTGTAGTTGGCGGTGTAGGAACCGATTTCGAACTCTACCTAGAACTTGTCTATCTCAAAACAGGAGCTAAACCACCGACTCCCATTTTCCTAATTGGACCTATTGAATACTGGAAAGAAAAAGTGGCCCACGCCTACGAGATCAACCTCAAAGCAGGAACCATCCGTGGATCCGAATGGATCAGCAACTGCCTATATTGTATCACTTCTCCGGAAGCTGGAATTGCCGTATTCGAACAATTCCTAGCTGGAGAACTCCCTATAGGATACGACTATCCTCCAGCTCCAGATGGATTAGTGATCGTCSEQ ID NO: 116 - CT387 fragment protein sequenceTLFHSHHDAVSPDSYLCSSLQLVGTGVYEGEIEIQNIPSYFLGFQLPSHCIHLNLKSSLAQLGIDASLLHCELSKNQHRAHIHAQFTGHGPIAESMLALLQPGDRVAKLFAADDRRLVRSPDYLESMLKNTDKAGHPLLCFGKKLEHLISFDVVDDRLVVSLPTLPGVVRYDSDIYGLLPLIQKSLSNPKLSIRHFLALYQQIVEGQHVSCGNHILLIKTEPLHIRTVFARVVNQLLPQGLSHTSANILEPTTRESGDIFEFFGNPSAQIERIPLEFFTIEPYKEHSYFCNRDLLQTILQSESEIKKIFETAPKEPVKAATYLSKGSEISSLHTDSWLTGSAAAYQYSEQADKNEYTHAQPCYPFLEAMEMGLINSEGALLTRYFPSASLKGMLISYHVRHYLKQIYFQVPSYTHGNYFSHNDRGLLLDLQQADIDVFWADEESGRVLQYTKRRDKNSGMFVIKNRVEEFRSAYFIAIYGSRLLENNFSAQLHTLLAGLQQAAHTLGIPGFSKPTPLAVITGGGTGVMATGNRVAKELGILSCGTVLDLEASPAQIDQPTNEFLDAKMTYRLPQLIERQEHFYADLPILVVGGVGTDFELYLELVYLKTGAKPPTPIFLIGPIEYWKEKVAHAYEINLKAGTIRGSEWISNCLYCITSPEAGIAVFEQFLAGELPIGYDYPPAPDGLVIVSEQ ID NO: 117 - CT812 fragment nucleotide sequenceTGCGTAGATCTTCATGCTGGAGGACAGTCTGTAAATGAGCTGGTATATGTAGGCCCTCAAGCGGTTTTATTGTTAGACCAAATTCGAGATCTATTCGTTGGGTCTAAAGATAGTCAGGCTGAAGGACAGTATAGGTTAATTGTAGGAGATCCAAGTTCTTTCCAAGAGAAAGATGCGGATACTCTTCCCGGGAAGGTAGAGCAAAGTACTTTGTTCTCAGTAACCAATCCCGTGGTTTTCCAAGGTGTGGACCAACAGGATCAAGTCTCTTCCCAAGGGTTAATTTGTAGTTTTACGAGCAGCAACCTTGATTCTCCTCGTGACGGAGAATCTTTTTTAGGTATTGCTTTTGTTGGGGATAGTAGTAAGGCTGGAATCACATTAACTGACGTGAAAGCTTCTTTGTCTGGAGCGGCTTTATATTCTACAGAAGATCTTATCTTTGAAAAGATTAAGGGTGGATTGGAATTTGCATCATGTTCTTCTCTAGAACAGGGGGGAGCTTGTGCAGCTCAAAGTATTTTGATTCATGATTGTCAAGGATTGCAGGTTAAACACTGTACTACAGCCGTGAATGCTGAGGGGTCTAGTGCGAATGATCATCTTGGATTTGGAGGAGGCGCTTTCTTTGTTACGGGTTCTCTTTCTGGAGAGAAAAGTCTCTATATGCCTGCAGGAGATATGGTAGTTGCGAATTGTGATGGGGCTATATCTTTTGAAGGAAACAGCGCGAACTTTGCTAATGGAGGAGCGATTGCTGCCTCTGGGAAAGTGCTTTTTGTCGCTAATGATAAAAAGACTTCTTTTATAGAGAACCGAGCTTTGTCTGGAGGAGCGATTGCAGCCTCTTCTGATATTGCCTTTCAAAACTGCGCAGAACTAGTTTTCAAAGGCAATTGTGCAATTGGAACAGAGGATAAAGGTTCTTTAGGTGGAGGGGCTATATCTTCTCTAGGCACCGTTCTTTTGCAAGGGAATCACGGGATAACTTGTGATAAGAATGAGTCTGCTTCGCAAGGAGGCGCCATTTTTGGCAAAAATTGTCAGATTTCTGACAACGAGGGGCCAGTGGTTTTCAGAGATAGTACAGCTTGCTTAGGAGGAGGCGCTATTGCAGCTCAAGAAATTGTTTCTATTCAGAACAATCAGGCTGGGATTTCCTTCGAGGGAGGTAAGGCTAGTTTCGGAGGAGGTATTGCGTGTGGATCTTTTTCTTCCGCAGGTGGTGCTTCTGTTTTAGGGACCATTGATATTTCGAAGAATTTAGGCGCGATTTCGTTCTCTCGTACTTTATGTACGACCTCAGATTTAGGACAAATGGAGTACCAGGGAGGAGGAGCTCTATTTGGTGAAAATATTTCTCTTTCTGAGAATGCTGGTGTGCTCACCTTTAAAGACAACATTGTGAAGACTTTTGCTTCGAATGGGAAAATTCTGGGAGGAGGAGCGATTTTAGCTACTGGTAAGGTGGAAATTACTAATAATTCCGAAGGAATTTCTTTTACAGGAAATGCGAGAGCTCCACAAGCTCTTCCAACTCAAGAGGAGTTTCCTTTATTCAGCAAAAAAGAAGGGCGACCACTCTCTTCAGGATATTCTGGGGGAGGAGCGATTTTAGGAAGAGAAGTAGCTATTCTCCACAACGCTGCAGTAGTATTTGAGCAAAATCGTTTGCAGTGCAGCGAAGAAGAAGCGACATTATTAGGTTGTTGTGGAGGAGGCGCTGTTCATGGGATGGATAGCACTTCGATTGTTGGCAACTCTTCAGTAAGATTTGGTAATAATTACGCAATGGGACAAGGAGTCTCAGGAGGAGCTCTTTTATCTAAAACAGTGCAGTTAGCTGGGAATGGAAGCGTCGATTTTTCTCGAAATATTGCTAGTTTGGGAGGAGGAGCTCTTCAAGCTTCTGAAGGAAATTGTGAGCTAGTTGATAACGGCTATGTGCTATTCAGAGATAATCGAGGGAGGGTTTATGGGGGTGCTATTTCTTGCTTACGTGGAGATGTAGTCATTTCTGGAAACAAGGGTAGAGTTGAATTTAAAGACAACATAGCAACACGTCTTTATGTGGAAGAAACTGTAGAAAAGGTTGAAGAGGTAGAGCCAGCTCCTGAGCAAAAAGACAATAATGAGCTTTCTTTCTTAGGGAGAGCAGAACAGAGTTTTATTACTGCAGCTAATCAAGCTCTTTTCGCATCTGAAGATGGGGATTTATCACCTGAGTCATCCATTTCTTCTGAAGAACTTGCGAAAAGAAGAGAGTGTGCTGGAGGAGCTATTTTTGCAAAACGGGTTCGTATTGTAGATAACCAAGAGGCCGTTGTATTCTCGAATAACTTCTCTGATATTTATGGCGGCGCCATTTTTACAGGTTCTCTTCGAGAAGAGGATAAGTTAGATGGGCAAATCCCTGAAGTCTTGATCTCAGGCAATGCAGGGGATGTTGTTTTTTCCGGAAATTCCTCGAAGCGTGATGAGCATCTTCCTCATACAGGTGGGGGAGCCATTTGTACTCAAAATTTGACGATTTCTCAGAATACAGGGAATGTTCTGTTTTATAACAACGTGGCCTGTTCGGGAGGAGCTGTTCGTATAGAGGATCATGGTAATGTTCTTTTAGAAGCTTTTGGAGGAGATATTGTTTTTAAAGGAAATTCTTCTTTCAGAGCACAAGGATCCGATGCTATCTATTTTGCAGGTAAAGAATCGCATATTACAGCCCTGAATGCTACGGAAGGACATGCTATTGTTTTCCACGACGCATTAGTTTTTGAAAATCTAGAAGAAAGGAAATCTGCTGAAGTATTGTTAATCAATAGTCGAGAAAATCCAGGTTACACTGGATCTATTCGATTTTTAGAAGCAGAAAGTAAAGTTCCTCAATGTATTCATGTACAACAAGGAAGCCTTGAGTTGCTAAATGGAGCCACATTATGTAGTTATGGTTTTAAACAAGATGCTGGAGCTAAGTTGGTATTGGCTGCTGGAGCTAAACTGAAGATTTTAGATTCAGGAACTCCTGTACAACAAGGGCATGCTATCAGTAAACCTGAAGCAGAAATCGAGTCATCTTCTGAACCAGAGGGTGCACATTCTCTTTGGATTGCGAAGAATGCTCAAACAACAGTTCCTATGGTTGATATCCATACTATTTCTGTAGATTTAGCCTCCTTCTCTTCTAGTCAACAGGAGGGGACAGTAGAAGCTCCTCAGGTTATTGTTCCTGGAGGAAGTTATGTTCGATCTGGAGAGCTTAATTTGGAGTTAGTTAACACAACAGGTACTGGTTATGAAAATCATGCTTTATTGAAGAATGAGGCTAAAGTTCCATTGATGTCTTTCGTTGCTTCTGGTGATGAAGCTTCAGCCGAAATCAGTAACTTGTCGGTTTCTGATTTACAGATTCATGTAGTAACTCCAGAGATTGAAGAAGACACATACGGCCATATGGGAGATTGGTCTGAGGCTAAAATTCAAGATGGAACTCTTGTCATTAGTTGGAATCCTACTGGATATCGATTAGATCCTCAAAAAGCAGGGGCTTTAGTATTTAATGCATTATGGGAAGAAGGGGCTGTCTTGTCTGCTCTGAAAAATGCACGCTTTGCTCATAATCTCACTGCTCAGCGTATGGAATTCGATTATTCTACAAATGTGTGGGGATTCGCCTTTGGTGGTTTCCGAACTCTATCTGCAGAGAATCTGGTTGCTATTGATGGATACAAAGGAGCTTATGGTGGTGCTTCTGCTGGAGTCGATATTCAATTGATGGAAGATTTTGTTCTAGGAGTTAGTGGAGCTGCTTTCCTAGGTAAAATGGATAGTCAGAAGTTTGATGCGGAGGTTTCTCGGAAGGGAGTTGTTGGTTCTGTATATACAGGATTTTTAGCTGGATCCTGGTTCTTCAAAGGACAATATAGCCTTGGAGAAACACAGAACGATATGAAAACGCGTTATGGAGTACTAGGAGAGTCGAGTGCTTCTTGGACATCTCGAGGAGTACTGGCAGATGCTTTAGTTGAATACCGAAGTTTAGTTGGTCCTGTGAGACCTACTTTTTATGCTTTGCATTTCAATCCTTATGTCGAAGTATCTTATGCTTCTATGAAATTCCCTGGCTTTACAGAACAAGGAAGAGAAGCGCGTTCTTTTGAAGACGCTTCCCTTACCAATATCACCATTCCTTTAGGGATGAAGTTTGAATTGGCGTTCATAAAAGGACAGTTTTCAGAGGTGAACTCTTTGGGAATAAGTTATGCATGGGAAGCTTATCGAAAAGTAGAAGGAGGCGCGGTGCAGCTTTTAGAAGCTGGGTTTGATTGGGAGGGAGCTCCAATGGATCTTCCTAGACAGGAGCTGCGTGTCGCTCTGGAAAATAATACGGAATGGAGTTCTTACTTCAGCACAGTCTTAGGATTAACAGCTTTTTGTGGAGGATTTACTTCTACAGATAGTAAACTAGGATATGAGGCGAATACTGGATTGCGATTGATCTTTSEQ ID NO: 118 - CT812 fragment protein sequenceCVDLHAGGQSVNELVYVGPQAVLLLDQIRDLFVGSKDSQAEGQYRLIVGDPSSFQEKDADTLPGKVEQSTLFSVTNPVVFQGVDQQDQVSSQGLICSFTSSNLDSPRDGESFLGIAFVGDSSKAGITLTDVKASLSGAALYSTEDLIFEKIKGGLEFASCSSLEQGGACAAQSILIHDCQGLQVKHCTTAVNAEGSSANDHLGFGGGAFFVTGSLSGEKSLYMPAGDMVVANCDGAISFEGNSANFANGGAIAASGKVLFVANDKKTSFIENRALSGGAIAASSDIAFQNCAELVFKGNCAIGTEDKGSLGGGAISSLGTVLLQGNHGITCDKNESASQGGAIFGKNCQISDNEGPVVFRDSTACLGGGAIAAQEIVSIQNNQAGISFEGGKASFGGGIACGSFSSAGGASVLGTIDISKNLGAISFSRTLCTTSDLGQMEYQGGGALFGENISLSENAGVLTFKDNIVKTFASNGKILGGGAILATGKVEITNNSEGISFTGNARAPQALPTQEEFPLFSKKEGRPLSSGYSGGGAILGREVAILHNAAVVFEQNRLQCSEEEATLLGCCGGGAVHGNDSTSIVGNSSVRFGNNYAMGQGVSGGALLSKTVQLAGNGSVDFSRNIASLGGGALQASEGNCELVDNGYVLFRDNRGRVYGGAISCLRGDVVISGNKGRVEFKDNIATRLYVEETVEKVEEVEPAPEQKDNNELSFLGRAEQSFITAANQALFASEDGDLSPESSISSEELAKRRECAGGAIFAKRVRIVDNQEAVVFSNNFSDIYGGAIFTGSLREEDKLDGQIPEVLISGNAGDVVFSGNSSKRDEHLPHTGGGAICTQNLTISQNTGNVLFYNNVACSGGAVRIEDHGNVLLEAFGGDIVFKGNSSFRAQGSDAIYFAGKESHITALNATEGHAIVFHDALVFENLEERKSAEVLLINSRENPGYTGSIRFLEAESKVPQCIHVQQGSLELLNGATLCSYGFKQDAGAKLVLAAGAKLKILDSGTPVQQGHAISKPEAEIESSSEPEGAHSLWIAKNAQTTVPMVDIHTISVDLASFSSSQQEGTVEAPQVIVPGGSYVRSGELNLELVNTTGTGYENHALLKNEAKVPLMSFVASGDEASAEISNLSVSDLQIHVVTPEIEEDTYGHMGDWSEAKIQDGTLVISWNPTGYRLDPQKAGALVFNALWEEGAVLSALKNARFAHNLTAQRMEFDYSTNVWGFAFGGFRTLSAENLVAIDGYKGAYGGASAGVDIQLMEDFVLGVSGAAFLGKMDSQKFDAEVSRKGVVGSVYTGFLAGSWFFKGQYSLGETQNDMKTRYGVLGESSASWTSRGVLADALVEYRSLVGPVRPTFYALHFNPYVEVSYASMKFPGFTEQGREARSFEDASLTNITIPLGMKFELAFIKGQFSEVNSLGISYAWEAYRKVEGGAVQLLEAGFDWEGAPMDLPRQELRVALENNTEWSSYFSTVLGLTAFCGGFTSTDSKLGYEANTGLRLIFSEQ ID NO: 119 - CT812N nucleotide sequenceTGCGTAGATCTTCATGCTGGAGGACAGTCTGTAAATGAGCTGGTATATGTAGGCCCTCAAGCGGTTTTATTGTTAGACCAAATTCGAGATCTATTCGTTGGGTCTAAAGATAGTCAGGCTGAAGGACAGTATAGGTTAATTGTAGGAGATCCAAGTTCTTTCCAAGAGAAAGATGCGGATACTCTTCCCGGGAAGGTAGAGCAAAGTACTTTGTTCTCAGTAACCAATCCCGTGGTTTTCCAAGGTGTGGACCAACAGGATCAAGTCTCTTCCCAAGGGTTAATTTGTAGTTTTACGAGCAGCAACCTTGATTCTCCTCGTGACGGAGAATCTTTTTTAGGTATTGCTTTTGTTGGGGATAGTAGTAAGGCTGGAATCACATTAACTGACGTGAAAGCTTCTTTGTCTGGAGCGGCTTTATATTCTACAGAAGATCTTATCTTTGAAAAGATTAAGGGTGGATTGGAATTTGCATCATGTTCTTCTCTAGAACAGGGGGGAGCTTGTGCAGCTCAAAGTATTTTGATTCATGATTGTCAAGGATTGCAGGTTAAACACTGTACTACAGCCGTGAATGCTGAGGGGTCTAGTGCGAATGATCATCTTGGATTTGGAGGAGGCGCTTTCTTTGTTACGGGTTCTCTTTCTGGAGAGAAAAGTCTCTATATGCCTGCAGGAGATATGGTAGTTGCGAATTGTGATGGGGCTATATCTTTTGAAGGAAACAGCGCGAACTTTGCTAATGGAGGAGCGATTGCTGCCTCTGGGAAAGTGCTTTTTGTCGCTAATGATAAAAAGACTTCTTTTATAGAGAACCGAGCTTTGTCTGGAGGAGCGATTGCAGCCTCTTCTGATATTGCCTTTCAAAACTGCGCAGAACTAGTTTTCAAAGGCAATTGTGCAATTGGAACAGAGGATAAAGGTTCTTTAGGTGGAGGGGCTATATCTTCTCTAGGCACCGTTCTTTTGCAAGGGAATCACGGGATAACTTGTGATAAGAATGAGTCTGCTTCGCAAGGAGGCGCCATTTTTGGCAAAAATTGTCAGATTTCTGACAACGAGGGGCCAGTGGTTTTCAGAGATAGTACAGCTTGCTTAGGAGGAGGCGCTATTGCAGCTCAAGAAATTGTTTCTATTCAGAACAATCAGGCTGGGATTTCCTTCGAGGGAGGTAAGGCTAGTTTCGGAGGAGGTATTGCGTGTGGATCTTTTTCTTCCGCAGGTGGTGCTTCTGTTTTAGGGACCATTGATATTTCGAAGAATTTAGGCGCGATTTCGTTCTCTCGTACTTTATGTACGACCTCAGATTTAGGACAAATGGAGTACCAGGGAGGAGGAGCTCTATTTGGTGAAAATATTTCTCTTTCTGAGAATGCTGGTGTGCTCACCTTTAAAGACAACATTGTGAAGACTTTTGCTTCGAATGGGAAAATTCTGGGAGGAGGAGCGATTTTAGCTACTGGTAAGGTGGAAATTACTAATAATTCCGAAGGAATTTCTTTTACAGGAAATGCGAGAGCTCCACAAGCTCTTCCAACTCAAGAGGAGTTTCCTTTATTCAGCAAAAAAGAAGGGCGACCACTCTCTTCAGGATATTCTGGGGGAGGAGCGATTTTAGGAAGAGAAGTAGCTATTCTCCACAACGCTGCAGTAGTATTTGAGCAAAATCGTTTGCAGTGCAGCGAAGAAGAAGCGACATTATTAGGTTGTTGTGGAGGAGGCGCTGTTCATGGGATGGATAGCACTTCGATTGTTGGCAACTCTTCAGTAAGATTTGGTAATAATTACGCAATGGGACAAGGAGTCTCAGGAGGAGCTCTTTTATCTAAAACAGTGCAGTTAGCTGGGAATGGAAGCGTCGATTTTTCTCGAAATATTGCTAGTTTGGGAGGAGGAGCTCTTCAAGCTTCTGAAGGAAATTGTGAGCTAGTTGATAACGGCTATGTGCTATTCAGAGATAATCGAGGGAGGGTTTATGGGGGTGCTATTTCTTGCTTACGTGGAGATGTAGTCATTTCTGGAAACAAGGGTAGAGTTGAATTTAAAGACAACATAGCAACACGTCTTTATGTGGAAGAAACTGTAGAAAAGGTTGAAGAGGTAGAGCCAGCTCCTGAGCAAAAAGACAATAATGAGCTTTCTTTCTTAGGGAGAGCAGAACAGAGTTTTATTACTGCAGCTAATCAAGCTCTTTTCGCATCTGAAGATGGGGATTTATCACCTGAGTCATCCATTTCTTCTGAAGAA SEQ ID NO: 120: CT812N protein sequenceCVDLHAGGQSVNELVYVGPQAVLLLDQIRDLFVGSKDSQAEGQYRLIVGDPSSFQEKDADTLPGKVEQSTLFSVTNPVVFQGVDQQDQVSSQGLICSFTSSNLDSPRDGESFLGIAFVGDSSKAGITLTDVKASLSGAALYSTEDLIFEKIKGGLEFASCSSLEQGGACAAQSILIHDCQGLQVKHCTTAVNAEGSSANDHLGFGGGAFFVTGSLSGEKSLYMPAGDMVVANCDGAISFEGNSANFANGGAIAASGKVLFVANDKKTSFIENRALSGGAIAASSDIAFQNCAELVFKGNCAIGTEDKGSLGGGAISSLGTVLLQGNHGITCDKNESASQGGAIFGKNCQISDNEGPVVFRDSTACLGGGAIAAQEIVSIQNNQAGISFEGGKASFGGGIACGSFSSAGGASVLGTIDISKNLGAISFSRTLCTTSDLGQMEYQGGGALFGENISLSENAGVLTFKDNIVKTFASNGKILGGGAILATGKVEITNNSEGISFTGNARAPQALPTQEEFPLFSKKEGRPLSSGYSGGGAILGREVAILHNAAVVFEQNRLQCSEEEATLLGCCGGGAVHGMDSTSIVGNSSVRFGNNYAMGQGVSGGALLSKTVQLAGNGSVDFSRNIASLGGGALQASEGNCELVDNGYVLFRDNRGRVYGGAISCLRGDVVISGNKGRVEFKDNIATRLYVEETVEKVEEVEPAPEQKDNNELSFLGRAEQSFITAANQALFASEDGDLSPESSISSEESEQ ID NO: 121: CT812C nucleotide sequenceGAAGAACTTGCGAAAAGAAGAGAGTGTGCTGGAGGAGCTATTTTTGCAAAACGGGTTCGTATTGTAGATAACCAAGAGGCCGTTGTATTCTCGAATAACTTCTCTGATATTTATGGCGGCGCCATTTTTACAGGTTCTCTTCGAGAAGAGGATAAGTTAGATGGGCAAATCCCTGAAGTCTTGATCTCAGGCAATGCAGGGGATGTTGTTTTTTCCGGAAATTCCTCGAAGCGTGATGAGCATCTTCCTCATACAGGTGGGGGAGCCATTTGTACTCAAAATTTGACGATTTCTCAGAATACAGGGAATGTTCTGTTTTATAACAACGTGGCCTGTTCGGGAGGAGCTGTTCGTATAGAGGATCATGGTAATGTTCTTTTAGAAGCTTTTGGAGGAGATATTGTTTTTAAAGGAAATTCTTCTTTCAGAGCACAAGGATCCGATGCTATCTATTTTGCAGGTAAAGAATCGCATATTACAGCCCTGAATGCTACGGAAGGACATGCTATTGTTTTCCACGACGCATTAGTTTTTGAAAATCTAGAAGAAAGGAAATCTGCTGAAGTATTGTTAATCAATAGTCGAGAAAATCCAGGTTACACTGGATCTATTCGATTTTTAGAAGCAGAAAGTAAAGTTCCTCAATGTATTCATGTACAACAAGGAAGCCTTGAGTTGCTAAATGGAGCCACATTATGTAGTTATGGTTTTAAACAAGATGCTGGAGCTAAGTTGGTATTGGCTGCTGGAGCTAAACTGAAGATTTTAGATTCAGGAACTCCTGTACAACAAGGGCATGCTATCAGTAAACCTGAAGCAGAAATCGAGTCATCTTCTGAACCAGAGGGTGCACATTCTCTTTGGATTGCGAAGAATGCTCAAACAACAGTTCCTATGGTTGATATCCATACTATTTCTGTAGATTTAGCCTCCTTCTCTTCTAGTCAACAGGAGGGGACAGTAGAAGCTCCTCAGGTTATTGTTCCTGGAGGAAGTTATGTTCGATCTGGAGAGCTTAATTTGGAGTTAGTTAACACAACAGGTACTGGTTATGAAAATCATGCTTTATTGAAGAATGAGGCTAAAGTTCCATTGATGTCTTTCGTTGCTTCTGGTGATGAAGCTTCAGCCGAAATCAGTAACTTGTCGGTTTCTGATTTACAGATTCATGTAGTAACTCCAGAGATTGAAGAAGACACATACGGCCATATGGGAGATTGGTCTGAGGCTAAAATTCAAGATGGAACTCTTGTCATTAGTTGGAATCCTACTGGATATCGATTAGATCCTCAAAAAGCAGGGGCTTTAGTATTTAATGCATTATGGGAAGAAGGGGCTGTCTTGTCTGCTCTGAAAAATGCACGCTTTGCTCATAATCTCACTGCTCAGCGTATGGAATTCGATTATTCTACAAATGTGTGGGGATTCGCCTTTGGTGGTTTCCGAACTCTATCTGCAGAGAATCTGGTTGCTATTGATGGATACAAAGGAGCTTATGGTGGTGCTTCTGCTGGAGTCGATATTCAATTGATGGAAGATTTTGTTCTAGGAGTTAGTGGAGCTGCTTTCCTAGGTAAAATGGATAGTCAGAAGTTTGATGCGGAGGTTTCTCGGAAGGGAGTTGTTGGTTCTGTATATACAGGATTTTTAGCTGGATCCTGGTTCTTCAAAGGACAATATAGCCTTGGAGAAACACAGAACGATATGAAAACGCGTTATGGAGTACTAGGAGAGTCGAGTGCTTCTTGGACATCTCGAGGAGTACTGGCAGATGCTTTAGTTGAATACCGAAGTTTAGTTGGTCCTGTGAGACCTACTTTTTATGCTTTGCATTTCAATCCTTATGTCGAAGTATCTTATGCTTCTATGAAATTCCCTGGCTTTACAGAACAAGGAAGAGAAGCGCGTTCTTTTGAAGACGCTTCCCTTACCAATATCACCATTCCTTTAGGGATGAAGTTTGAATTGGCGTTCATAAAAGGACAGTTTTCAGAGGTGAACTCTTTGGGAATAAGTTATGCATGGGAAGCTTATCGAAAAGTAGAAGGAGGCGCGGTGCAGCTTTTAGAAGCTGGGTTTGATTGGGAGGGAGCTCCAATGGATCTTCCTAGACAGGAGCTGCGTGTCGCTCTGGAAAATAATACGGAATGGAGTTCTTACTTCAGCACAGTCTTAGGATTAACAGCTTTTTGTGGAGGATTTACTTCTACAGATAGTAAACTAGGATATGAGGCGAATACTGGATTGCGATTGATCTTT SEQ ID NO: 122: CT812C protein sequenceEELAKRRECAGGAIFAKRVRIVDNQEAVVFSNNFSDIYGGAIFTGSLREEDKLDGQIPEVLISGNAGDVVFSGNSSKRDEHLPHTGGGAICTQNLTISQNTGNVLFYNNVACSGGAVRIEDHGNVLLEAFGGDIVFKGNSSFRAQGSDAIYFAGKESHITALNATEGHAIVFHDALVFENLEERKSAEVLLINSRENPGYTGSIRFLEAESKVPQCIHVQQGSLELLNGATLCSYGFKQDAGAKLVLAAGAKLKILDSGTPVQQGHAISKPEAEIESSSEPEGAHSLWIAKNAQTTVPMVDIHTISVDLASFSSSQQEGTVEAPQVIVPGGSYVRSGELNLELVNTTGTGYENHALLKNEAKVPLMSFVASGDEASAEISNLSVSDLQIHVVTPEIEEDTYGHMGDWSEAKIQDGTLVISWNPTGYRLDPQKAGALVFNALWEEGAVLSALKNARFAHNLTAQRMEFDYSTNVWGFAFGGFRTLSAENLVAIDGYKGAYGGASAGVDIQLMEDFVLGVSGAAFLGKMDSQKFDAEVSRKGVVGSVYTGFLAGSWFFKGQYSLGETQNDMKTRYGVLGESSASWTSRGVLADALVEYRSLVGPVRPTFYALHFNPYVEVSYASMKFPGFTEQGREARSFEDASLTNITIPLGMKFELAFIKGQFSEVNSLGISYAWEAYRKVEGGAVQLLEAGFDWEGAPMDLPRQELRVALENNTEWSSYFSTVLGLTAFCGGFTSTDSKLGYEANTGLRLIFSEQ ID NO: 123: CT869 fragment nucleotide sequenceAGAGAGGTTCCTTCTAGAATCTTTCTTATGCCCAACTCAGTTCCAGATCCTACGAAAGAGTCGCTATCAAATAAAATTAGTTTGACAGGAGACACTCACAATCTCACTAACTGCTATCTCGATAACCTACGCTACATACTGGCTATTCTACAAAAAACTCCCAATGAAGGAGCTGCTGTCACAATAACAGATTACCTAAGCTTTTTTGATACACAAAAAGAAGGTATTTATTTTGCAAAAAATCTCACCCCTGAAAGTGGTGGTGCGATTGGTTATGCGAGTCCCAATTCTCCTACCGTGGAGATTCGTGATACAATAGGTCCTGTAATCTTTGAAAATAATACTTGTTGCAGACTATTTACATGGAGAAATCCTTATGCTGCTGATAAAATAAGAGAAGGCGGAGCCATTCATGCTCAAAATCTTTACATAAATCATAATCATGATGTGGTCGGATTTATGAAGAACTTTTCTTATGTCCAAGGAGGAGCCATTAGTACCGCTAATACCTTTGTTGTGAGCGAGAATCAGTCTTGTTTTCTCTTTATGGACAACATCTGTATTCAAACTAATACAGCAGGAAAAGGTGGCGCTATCTATGCTGGAACGAGCAATTCTTTTGAGAGTAATAACTGCGATCTCTTCTTCATCAATAACGCCTGTTGTGCAGGAGGAGCGATCTTCTCCCCTATCTGTTCTCTAACAGGAAATCGTGGTAACATCGTTTTCTATAACAATCGCTGCTTTAAAAATGTAGAAACAGCTTCTTCAGAAGCTTCTGATGGAGGAGCAATTAAAGTAACTACTCGCCTAGATGTTACAGGCAATCGTGGTAGGATCTTTTTTAGTGACAATATCACAAAAAATTATGGCGGAGCTATTTACGCTCCTGTAGTTACCCTAGTGGATAATGGCCCTACCTACTTTATAAACAATATCGCCAATAATAAGGGGGGCGCTATCTATATAGACGGAACCAGTAACTCCAAAATTTCTGCCGACCGCCATGCTATTATTTTTAATGAAAATATTGTGACTAATGTAACTAATGCAAATGGTACCAGTACGTCAGCTAATCCTCCTAGAAGAAATGCAATAACAGTAGCAAGCTCCTCTGGTGAAATTCTATTAGGAGCAGGGAGTAGCCAAAATTTAATTTTTTATGATCCTATTGAAGTTAGCAATGCAGGGGTCTCTGTGTCCTTCAATAAGGAAGCTGATCAAACAGGCTCTGTAGTATTTTCAGGAGCTACTGTTAATTCTGCAGATTTTCATCAACGCAATTTACAAACAAAAACACCTGCACCCCTTACTCTCAGTAATGGTTTTCTATGTATCGAAGATCATGCTCAGCTTACAGTGAATCGATTCACACAAACTGGGGGTGTTGTTTCTCTTGGGAATGGAGCAGTTCTGAGTTGCTATAAAAATGGTACAGGAGATTCTGCTAGCAATGCCTCTATAACACTGAAGCATATTGGATTGAATCTTTCTTCCATTCTGAAAAGTGGTGCTGAGATTCCTTTATTGTGGGTAGAGCCTACAAATAACAGCAATAACTATACAGCAGATACTGCAGCTACCTTTTCATTAAGTGATGTAAAACTCTCACTCATTGATGACTACGGGAACTCTCCTTATGAATCCACAGATCTGACCCATGCTCTGTCATCACAGCCTATGCTATCTATTTCTGAAGCTAGCGATAACCAGCTACAATCAGAAAATATAGATTTTTCGGGACTAAATGTCCCTCATTATGGATGGCAAGGACTTTGGACTTGGGGCTGGGCAAAAACTCAAGATCCAGAACCAGCATCTTCAGCAACAATCACTGATCCACAAAAAGCCAATAGATTTCATAGAACCTTACTACTAACATGGCTTCCTGCCGGGTATGTTCCTAGCCCAAAACACAGAAGTCCCCTCATAGCTAACACCTTATGGGGGAATATGCTGCTTGCAACAGAAAGCTTAAAAAATAGTGCAGAGCTGACACCTAGTGGTCATCCTTTCTGGGGAATTACAGGAGGAGGACTAGGCATGATGGTTTACCAAGATCCTCGAGAAAATCATCCTGGATTCCATATGCGCTCTTCCGGATACTCTGCGGGGATGATAGCAGGGCAGACACACACCTTCTCATTGAAATTCAGTCAGACCTACACCAAACTCAATGAGCGTTACGCAAAAAACAACGTATCTTCTAAAAATTACTCATGCCAAGGAGAAATGCTCTTCTCATTGCAAGAAGGTTTCTTGCTGACTAAATTAGTTGGGCTTTACAGCTATGGAGACCATAACTGTCACCATTTCTATACTCAAGGAGAAAATCTAACATCTCAAGGGACGTTCCGCAGTCAAACGATGGGAGGTGCTGTCTTTTTTGATCTCCCTATGAAACCCTTTGGATCAACGCATATACTGACAGCTCCCTTTTTAGGTGCTCTTGGTATTTATTCTAGCCTGTCTCACTTTACTGAGGTGGGAGCCTATCCGCGAAGCTTTTCTACAAAGACTCCTTTGATCAATGTCCTAGTCCCTATTGGAGTTAAAGGTAGCTTTATGAATGCTACCCACAGACCTCAAGCCTGGACTGTAGAATTGGCATACCAACCCGTTCTGTATAGACAAGAACCAGGGATCGCAGCCCAGCTCCTAGCCAGTAAGGGTATTTGGTTCGGTAGTGGAAGCCCCTCATCGCGTCATGCCATGTCCTATAAAATCTCACAGCAAACACAACCTTTGAGTTGGTTAACTCTCCATTTCCAGTATCATGGATTCTACTCCTCTTCAACCTTCTGTAATTATCTCAATGGGGAAATTGCTCTGCGATTCSEQ ID NO: 124: CT869 fragment protein sequenceREVPSRIFLMPNSVPDPTKESLSNKISLTGDTHNLTNCYLDNLRYILAILQKTPNEGAAVTITDYLSFFDTQKEGIYFAKNLTPESGGAIGYASPNSPTVEIRDTIGPVIFENNTCCRLFTWRNPYAADKIREGGAIHAQNLYINHNHDVVGFMKNFSYVQGGAISTANTFVVSENQSCFLFMDNICIQTNTAGKGGAIYAGTSNSFESNNCDLFFINNACCAGGAIFSPICSLTGNRGNIVFYNNRCFKNVETASSEASDGGAIKVTTRLDVIGNRGRIFFSDNITKNYGGAIYAPVVTLVDNGPTYFINNIANNKGGAIYIDGTSNSKISADRHAIIFNENIVTNVTNANGTSTSANPPRRNAITVASSSGEILLGAGSSQNLIFYDPIEVSNAGVSVSFNKEADQTGSVVFSGATVNSADFHQRNLQTKTPAPLTLSNGFLCIEDHAQLTVNRFTQTGGVVSLGNGAVLSCYKNGTGDSASNASITLKHIGLNLSSILKSGAEIPLLWVEPTNNSNNYTADTAATFSLSDVKLSLIDDYGNSPYESTDLTHALSSQPMLSISEASDNQLQSENIDFSGLNVPHYGWQGLWTWGWAKTQDPEPASSATITDPQKANRFHRTLLLTWLPAGYVPSPKHRSPLIANTLWGNMLLATESLKNSAELTPSGHPFWGITGGGLGMMVYQDPRENHPGFHMRSSGYSAGMIAGQTHTFSLKFSQTYTKLNERYAKNNVSSKNYSCQGEMLFSLQEGFLLTKLVGLYSYGDHNCHHFYTQGENLTSQGTFRSQTMGGAVFFDLPMKPFGSTHILTAPFLGALGIYSSLSHFTEVGAYPRSFSTKTPLINVLVPIGVKGSFMNATHRPQAWTVELAYQPVLYRCEPGIAAQLLASKGIWFGSGSPSSRHAMSYKISQQTQPLSWLTLHFQYHGFYSSSTFCNYLNGEIALRFSEQ ID NO: 125: CT166 fragment nucleotide sequenceAACGTTCGTACGTACTCTGTTCAGAGGGGGGGGGTAAAAACGATTTCTGCTAGTGCAGTTCCTCCTACAGCAGCTGTTTTATCGAGAAAAAAGCGTGCTATAGAAGAGAAGAAGGAGGAAGCTTCTTCTGGAAAGATAGAAAATCTTGATGCTAGCAAATACGATCTTACTCCCAAGAACATAGAAGAAAAACTAGGAATTACTCCTGAACAGAAATCTACTGTTAAAGACCTATTAAATAAACTGAAAAAGGTCATTAGTGCTTACAACTCTATGCCAGATAAAAATTCGGAAGCGGGACAGAATTCCTTGATTCAACAAGGAAAATACGTCGATGCCATTCAGAAGAAGCTTCCAGCATCATCGCAGGCTCAGCCTAAACAGGCAAAAGCTAAGGAACAGAAAGCCGAAGAAAAACCTAAGACGACTCCGATTGAAGGTGTTCTTGAAACCATCAAAACAGAATTTAAAGGCCATCGTGTACCTGTTGAGAAAATCATCCATGGAATATGGATCGCAGGAGCGCCTCCGGATGGTATCGAAGATTATATGCGAGTCTTTTTAGATACTTATGAAGGTTTTGACTTCTACTTCTGGGTAGATGAGAATGCTTATGCAGCAGCTAAATTTTCTAGCATTTTGAAGAAGGTCGCTTTCGATGCGGCTATTCAAGATCTACGATCTGCCACAGATGAGTCTACGAAGGCCTTTGTTAAAGACTACGATGAATTAAAACAGAAATATGAAAAGAAAGTTGCGGAGACGACTTCTCAAGCAGAAAAAGACCAATATCTCAAAGATCTAAAGGATCTTTTAGAGAAATTTACAAAAATCAGTGATGAGATTCGTGGAAAATTTGATCGGCTGTTTCTTAAGAATGTGATTGTTGCTCAGAACGGATTCTTTAATTTCTGCTTGCTGAAAGGCCTCGGCAATATCAATGACGAAACGCGTGCAGAGTATTTAGAGAAAGAACTCAAACTTCCTACTGAGGAGATCGAACAGTATAAAAAGCTTAAAGAGACGAACAAAGAGAAGATAGCCGCTATTGTAAAACAACTAAACGAGAAACTTGGATCGGATCGGGTAAAAATCAAAGACATTAAAGAGCTGCAATCTATGAAGCAAGCTCGAAATGTCTACAATTATGAACAGGAAATGTTTCTGCGCTGGAACTATGCAGCCGCAACAGATCAGATTCGTATGTATATGTTGGAGGAACTTGGAGGTCTTTATACTGATCTGGATATGATGCCTTCATACTCTCAGGAAGTATTGGAGCTTATCAAAAAGCACAGTGATGGAAACCGAATGTTTGAGGATATGAGCTCTAGACGGGCGATTTCTGATGCGGTTTTAAAGATGGCTGTAGGTAAGGCGACAACAGTTTCCATGGAAGAGGTAGCAAAGGATATCGATGTTTCTCGCTTAACAGAAGAGGATAAGACAAAATTAAATGCTCTATTTAAGGATCTAGAGCCATTTGCAAAACCGGATTCTAAAGGAGCTGAAGCAGAAGGGGGTGAAGGAGCAAAAGGTATGAAAAAGAGCTTTTTCCAGCCCATAGATCTGAATATTGTCAGAAATACCATGCCTATCTTGAGACGCTATCATCACTATCCTGAGTTAGGATGGTTTATTCGAGGATTGAACGGATTGATGGTCTCTCATAAGGGAAGCACTGCGGTTTCTGCTGTCATTGTAGGGCAACAGGCTGCCTACCAGGAACTAGCAGCACTTAGACAAGATGTCCTTTCAGGGGAGTTTTTCCATTCTTTAGAAAATTTGACACATAGAAACCATAAGGAGCGTATTGGAAATCATCTCGTCGCTAATTATTTGGCTAAAAGTCTCTTTTTTGATTACTGCCAAGATTCAGTGATGCCGGAGGCTGTAAGTACCTTAGGTATTAGASEQ ID NO: 126 - CT166 fragment protein sequenceNVRTYSVQRGGVKTISASAVPPTAAVLSRKKRAIEEKKEEASSGKIENLDASKYDLTPKNIEEKLGITPEQKSTVKDLLNKLKKVISAYNSMPDKNSEAGQNSLIQQGKYVDAIQKKLPASSQAQPKQAKAKEQKAEEKPKTTPIEGVLETIKTEFKGHRVPVEKIIHGIWIAGAPPDGIEDYMRVFLDTYEGFDFYFWVDENAYAAAKFSSILKKVAFDAAIQDLRSATDESTKAFVKDYDELKQKYEKKVAETTSQAEKDQYLKDLKDLLEKFTKISDEIRGKFDRLFLKNVIVAQNGFFNFCLLKGLGNINDETRAEYLEKELKLPTEEIEQYKKLKETNKEKIAAIVKQLNEKLGSDRVKIKDIKELQSMKQARNVYNYEQEMFLRWNYAAATDQIRMYMLEELGGLYTDLDMMPSYSQEVLELIKKHSDGNRMFEDMSSRRAISDAVLKMAVGKATTVSMEEVAKDIDVSRLTEEDKTKLNALFKDLEPFAKPDSKGAEAEGGEGAKGMKKSFFQPIDLNIVRNTMPILRRYHHYPELGWFIRGLNGLMVSHKGSTAVSAVIVGQQAAYQELAALRQDVLSGEFFHSLENLTHRNHKERIGNHLVANYLAKSLFFDYCQDSVMPEAVSTLGIRSEQ ID NO: 127 - CT175 fragment nucleotide sequenceTGTTATCATAAAAAAGAAGAACCAAAAGATGTTTTGCGGATTGCGATCTGTCATGATCCAATGTCTTTAGATCCGCGTCAGGTTTTTTTAAGCAAAGATGTTTCTATTGTAAAAGCTCTCTATGAAGGGTTAGTCCGGGAAAAAGAAGCTGCGTTCCAGCTAGCTTTGGCAGAAAGATATCATCAATCTGATGATGGTTGTGTTTATACTTTTTTTCTAAAAAATACATTCTGGAGCAACGGAGATGTTGTAACAGCATATGATTTTGAAGAGTCTATTAAACAAATTTATTTCCGAGAAATTGATAACCCTTCGTTACGCTCTCTTGCATTAATTAAAAATTCTCATGCTGTTTTAACAGGAGCTCTCCCTGTTGAAGATTTAGGTGTTAGAGCTTTGAATGCGAAAACTCTAGAAATTGTTTTAGAAAACCCGTTTCCTTATTTTCTAGAGATATTGGCGCACCCGGTTTTTTATCCGGTGCACACCTCTTTACGAGAATATTACAAAGATAAGCGTAACAAACGCGTTTTCCCGATAATTTCTAATGGTCCTTTTGCGATTCAATGTTATGAGCCGCAAAGATATTTACTAATCAACAAAAACCCTCTGTATCATGCCAAGCACGATGTTCTGTTAAATTCGGTATGTTTGCAGATAGTTCCTGATATCCATACAGCTATGCAGTTATTCCAAAAAAATCATATCGATTTAGTTGGGTTACCCTGGAGCTCCTCCTTTTCTTTAGAAGAACAAAGAAATCTCCCTAGAGAAAAATTATTTGATTATCCTGTATTGAGTTGCTCTGTTTTATTCTGTAACATTCATCAAACACCTTTAAATAATCCCTCGCTGAGAACAGCCCTCTCTTTAGCAATCAATCGAGAAACTTTATTAAAACTAGCAGGTAAAGGCTGTAGCGCTACGAGCTTTGTTCACCCACAATTATCTCAGATACCTGCTACTACTTTGTCTCAAGATGAGCGGATTGCTTTAGCAAAAGGCTACTTGACCGAAGCTTTAAAGACTTTATCTCAAGAAGATTTAGAAAAAATTACATTAATTTATCCTATAGAATCTGTTTGCTTACGAGCCGTTGTTCAAGAAATTCGCCAACAATTATTTGATGTACTGGGATTTAAAATTTCTACATTAGGATTAGAATATCATTGTTTTTTAGACAAACGTTCCAGAGGAGAATTCTCCTTAGCAACTGGTAATTGGATTGCAGACTATCATCAAGCTAGTGCTTTCCTGTCTGTCCTAGGTAATGGGACAAGATATAAAGACTTTCAATTGATTAACTGGCAGAACCAAAAGTACACAAATATAGTTGCTCAACTTCTGATTCAAGAATCAAGCGACCTACAGCTTATGGCAGAGCAGTTGTTGCTTAAAGAAAGTCCTCTTATTCCTCTATACCACCTCGATTATGTGTATGCGAAACAGCCTCGGGTGTCTGATCTCCAAACCTCTTCTCGTGGAGAAATTGATTTAAAAAGAGTTTCATTAGCTGAAGGATAGSEQ ID NO: 128 - CT175 fragment protein sequenceCYHKKEEPKDVLRIAICHDPMSLDPRQVFLSKDVSIVKALYEGLVREKEAAFQLALAERYHQSDDGCVYTFFLKNTFWSNGDVVTAYDFEESIKQIYFREIDNPSLRSLALIKNSHAVLTGALPVEDLGVRALNAKTLEIVLENPFPYFLEILAHPVFYPVHTSLREYYKDKRNKRVFPIISNGPFAIQCYEPQRYLLINKNPLYHAKHDVLLNSVCLQIVPDIHTAMQLFQKNHIDLVGLPWSSSFSLEEQRNLPREKLFDYPVLSCSVLFCNIHQTPLNNPSLRTALSLAINRETLLKLAGKGCSATSFVHPQLSQIPATTLSQDERIALAKGYLTEALKTLSQEDLEKITLIYPIESVCLRAVVQEIRQQLFDVLGFKISTLGLEYHCFLDKRSRGEFSLATGNWIADYHQASAFLSVLGNGTRYKDFQLINWQNQKYTNIVAQLLIQESSDLQLMAEQLLLKESPLIPLYHLDYVYAKQPRVSDLQTSSRGEIDLKRVSLAEGSEQ ID NO: 129 - TC0666 fragment nucleotide sequence (homologue of CT387)ATGACACTCTTTCACACTCATCACGATGCCGTCTCTCCGGACGGCTACTTATGTTCTTCCCTTCAGTTAGTTGGCTCTGGCACATATGAAGGAGAAATCGAAATCCAAAATATTCCTTCTTATTTCCTTGGATTCCGATTACCCACCCATTGCGTTCATCTTAATTTGAAGAGTTCTCTAGCCCAGTTAGGAGTAGATGCATCTCTTCTTCACTGCGAACTAAGCAAAAATCAACAACGTGCACATATGCACGTGCAGTTCACCGGCTATGGCCCTATCGCTGAGTCCATGCTATCTCTTCTCAAACCCGGAGATCGAGTAGCCAAACTGTTTGCTGCAGATGATCGTAGACTAGTCCGCTCCCCTGATTATCTTGAAAGCATGCTAAAAAATACTGATAAGACAGGACATCCTCTGCTCCGATTTGGAAAAAAACTCGAGCATCTTATCTCTTTTGATGTGGTGGACGATCGCCTCGTTGTATCACTCCCCACCTTGCCAGGCATAGTCAATTATGACCCAGACATCTATGGACTTCTTCCCTTAATTCAAAAATCACTAAGCAATCCTAAATTGAGTATTCGCCACTTCTTGTCTCTCTATCAGAAGATCGTAGAAGGACCACACATCCCTTATGAAGGAAACATTTTGTTAATCAAAACAGAGCCTCTTCATATCCGCACAGTATTTGCTCGCGTGGTCGATCAAATGCTCCCTCAAGGTCTATTTCACACTTCTGCCAACATTTTAGAACCCACAACGCGAGAGTCTGGAGATATTTTTGAATTTTTTGGAAATCCCTCCACTCTTGTAGAAAGAATCCCTCTAGAATTCTTCACTATCGAACCCTACAAAGAACACTCTTACTTCTGTAATCGAGATCTATTGCAAACTACCTTGCAATCGGAAAGTGAAATCAAAAAAATATTCGATACAGCTCCTCAAGAGCCTGTAAAAGCCGCCACTTATTTATCAAAAGGAAGTGAAATTTCTTCTCTTGATGCAGATTCTTGGCTTACGGGATCCGCAGCTGCATACCAATGTAGCGAAAAACAGGCAGCTAAAGACGAATACATCCACGCTCAACCCTGTTATCCATTTTTGGAAGCAATGGAAACGGGACTCATCAATAGCGAAGGAGCTTTACTCACTCGGTTTTTCCCCTCTTCCAGCTTAAAAGGGATGTTGATCTCCTATCATGTACGCCACTATCTTAAGCAAATTTACTTTCAAGTTCCTTCTTATACATATGGAGACTACTTCTCTCATAATGACCGAGGATTACTGTTAGATCTATATCAGGCGAACATTGATGTGTTCTGGGCTGATGAAGAGAGCGGCCGTGTATTGCAATATACAAAACGGCGCGACAAAAATAGTGGAATGTTCGTCGTTAAAAATCGAGTAGAAGAGTTCCAATCAGCATATTTCGTAGCGATTTATGGATCACGTCTCCTGGAAAATAATTTCTCGGCCCAACTAAACACGCTTCTTGCAGGGTTACAAAAAGCTGCACACACTCTAGGCATTCCAGGCTTCTCAAAACCCACTCCTCTTGCCGTAATCACAGGAGGAGGGACTGGCGTTATGGCTACAGGAAATCGTGTTGCAAAAGAGTTGGGAATTCTTTCTTGCGGGACCGTTCTCGATTTGGAAGCTTCACCTGCACAAATAGATCAGCCTGCAAACGAATTTTTAGATGCCAAAATGACATACCGTCTACCGCAACTTATAGAAAGACAAGAACATTTTTATTCAGACCTTGCCATTTTAGTTGTTGGTGGTGTTGGAACAGATTTCGAACTTTACCTAGAACTCGTCTACTTGAAAACAGGCGCCAAACCTCCTACTCCAATTTTCCTTATTGGGCCTGTTGAATACTGGAAAGAGAAAGTTGCTCATGCCTATGAGATTAATCTTAAAGCAGGAACTATTCGTGGTTCTGAGTGGATCAGCAACTGCTTATTCTGCATTACATCTCCTGAAGCAGGAATTGCTGTATTCGAACAGTTCCTCGCTGGAGAACTTCCCATAGGATATGATTATCCTCCAGCTCCAGACGGATTAGTTATCGTCSEQ ID NO: 130 - TC0666 fragment protein sequence (homologue of CT387)MTLFHTHHDAVSPDGYLCSSLQLVGSGTYEGEIEIQNIPSYFLGFRLPTHCVHLNLKSSLAQLGVDASLLHCELSKNQQRAHMHVQFTGYGPIAESMLSLLKPGDRVAKLFAADDRRLVRSPDYLESMLKNTDKTGHPLLRFGKKLEHLISFDVVDDRLVVSLPTLPGIVNYDPDIYGLLPLIQKSLSNPKLSIRHFLSLYQKIVEGPHIPYEGNILLIKTEPLHIRTVFARVVDQMLPQGLFHTSANILEPTTRESGDIFEFFGNPSTLVERIPLEFFTIEPYKEHSYFCNRDLLQTTLQSESEIKKIFDTAPQEPVKAATYLSKGSEISSLDADSWLTGSAAAYQCSEKQAAKDEYIHAQPCYPFLEAMETGLINSEGALLTRFFPSSSLKGMLISYHVRHYLKQIYFQVPSYTYGDYFSHNDRGLLLDLYQANIDVFWADEESGRVLQYTKRRDKNSGMFVVKNRVEEFQSAYFVAIYGSRLLENNFSAQLNTLLAGLQKAAHTLGIPGFSKPTPLAVITGGGTGVMATGNRVAKELGILSCGTVLDLEASPAQIDQPANEFLDAKMTYRLPQLIERQEHFYSDLAILVVGGVGTDFELYLELVYLKTGAKPPTPIFLIGPVEYWKEKVAHAYEINLKAGTIRGSEWISNCLFCITSPEAGIAVFEQFLAGELPIGYDYPPAPDGLVIVSEQ ID NO: 131 - TC0197 fragment nucleotide sequenceAATTGTTCCGATCTTTATGCCGTAGGAAGTTCTGCAGACCATCCTGCCTACTTGATTCCTCAAGCGGGGTTATTATTGGATCATATTAAGGATATATTCATTGGCCCTAAAGATAGTCAGGATAAGGGGCAGTATAAGTTGATTATTGGTGAGGCTGGCTCTTTCCAAGATAGTAATGCAGAGACTCTTCCTCAAAAGGTAGAGCACAGCACTTTGTTTTCAGTTACAACACCTATAATTGTGCAAGGAATAGATCAACAAGATCAGGTCTCTTCGCAGGGATTGGTCTGTAATTTTTCAGGAGATCATTCAGAGGAGATTTTTGAGAGAGAATCCTTTTTAGGGATCGCTTTCCTAGGGAATGGTAGCAAGGATGGAATCACGTTAACAGATATAAAATCTTCGTTATCTGGTGCTGCCTTGTATTCTTCAGATGATCTTATTTTTGAAAGAATTAAGGGAGATATAGAGCTTTCTTCTTGTTCATCTTTAGAAAGAGGAGGAGCTTGTTCAGCTCAAAGTATTTTAATTCATGATTGTCAAGGATTAACGGTAAAACATTGTGCCGCAGGGGTGAATGTTGAAGGAGTTAGTGCTAGCGACCATCTCGGATTTGGGGGCGGGGCCTTCTCTACTACAAGTTCTCTTTCTGGAGAGAAGAGTTTGTATATGCCTGCAGGCGATATTGTGGTGGCTACCTGCGATGGTCCTGTGTGTTTCGAAGGAAATAGTGCTCAGTTAGCAAATGGTGGCGCTATTGCCGCTTCTGGTAAAGTTCTTTTTGTAGCTAACGAAAAAAAGATTTCCTTTACAGACAACCAAGCTTTGTCTGGAGGAGCTATTTCTGCATCTTCTAGTATTTCTTTCCAAAATTGTGCTGAGCTTGTGTTCAAGAGTAATCTTGCAAAAGGAGTTAAAGATAAATGTTCTTTGGGAGGAGGTGCTTTAGCCTCTTTAGAATCCGTAGTTTTGAAAGATAATCTCGGTATTACTTATGAAAAAAATCAGTCCTATTCGGAAGGAGGGGCTATTTTTGGGAAGGATTGTGAGATTTTTGAAAACAGGGGGCCTGTTGTATTCAGAGATAATACAGCTGCTTTAGGAGGCGGAGCTATTTTGGCGCAACAAACTGTGGCGATTTGTGGTAATAAGTCTGGAATATCTTTTGAAGGAAGTAAGTCTAGTTTTGGAGGGGCCATTGCTTGTGGAAATTTCTCTTCTGAGAATAATTCTTCAGCTTTGGGATCAATTGATATCTCTAACAATCTAGGAGATATCTCTTTTCTTCGGACTCTGTGTACTACTTCGGATTTAGGGCAAACGGATTACCAAGGGGGAGGGGCCTTATTCGCTGAAAATATTTCTCTTTCTGAGAATGCTGGTGCAATTACTTTCAAAGACAATATTGTGAAGACATTTGCCTCAAATGGAAAAATGTTGGGTGGAGGGGCAATTTTAGCTTCAGGAAATGTTTTGATTAGCAAAAACTCTGGAGAGATTTCTTTTGTAGGGAATGCTCGAGCTCCTCAGGCTATTCCGACTCGTTCATCTGACGAATTGTCTTTTGGCGCACAATTAACTCAAACTACTTCAGGATGTTCTGGAGGAGGAGCTCTTTTTGGTAAAGAGGTTGCCATTGTTCAAAATGCCACTGTTGTATTCGAGCAAAATCGCTTACAGTGTGGCGAGCAGGAAACACATGGTGGAGGCGGTGCTGTTTATGGTATGGAGAGTGCCTCTATTATTGGAAACTCTTTTGTGAGATTCGGAAATAATTACGCTGTAGGGAATCAGATTTCTGGAGGAGCTCTTTTATCCAAGAAGGTCCGTTTAGCTGAAAATACAAGGGTAGATTTTTCTCGAAATATCGCTACTTTCTGCGGCGGGGCTGTTCAAGTTTCTGATGGAAGTTGCGAATTGATCAACAATGGGTATGTGCTATTCAGAGATAACCGAGGGCAGACATTTGGTGGGGCTATTTCTTGCTTGAAAGGAGATGTGATCATTTCCGGAAATAAAGATAGGGTTGAGTTTAGAGATAACATTGTGACGCGGCCTTATTTTGAAGAAAATGAAGAAAAAGTTGAGACAGCAGATATTAATTCAGATAAGCAAGAAGCAGAAGAGCGCTCTTTATTAGAGAACATTGAGCAGAGCTTTATTACTGCAACTAATCAGACCTTTTTCTTAGAGGAAGAGAAACTCCCATCAGAAGCTTTTATCTCTGCTGAAGAACTTTCAAAGAGAAGAGAATGTGCTGGTGGGGCGATTTTTGCAAAACGGGTCTACATTACGGATAATAAAGAACCTATCTTGTTTTCGCATAATTTTTCTGATGTTTATGGGGGAGCTATTTTTACGGGTTCTCTACAGGAAACTGATAAACAAGATGTTGTAACTCCTGAAGTTGTGATATCAGGCAACGATGGGGATGTCATTTTTTCTGGAAATGCAGCTAAACATGATAAGCATTTACCTGATACAGGTGGTGGAGCCATTTGTACACAGAATTTGACGATTTCCCAAAACAATGGGAATGTCTTGTTCTTGAACAATTTTGCTTGTTCTGGTGGAGCAGTTCGCATAGAGGATCATGGAGAAGTTCTTTTAGAGGCTTTTGGGGGAGATATTATTTTCAATGGAAACTCTTCTTTCAGAGCTCAAGGATCGGATGCGATCTATTTTGCTGGTAAGGACTCTAGAATTAAAGCTTTAAATGCTACTGAAGGACATGCGATTGTGTTCCAAGATGCATTGGTGTTTGAAAATATAGAAGAAAGAAAGTCTTCGGGACTATTGGTGATTAACTCTCAGGAAAATGAGGGTTATACGGGATCCGTCCGATTTTTAGGATCTGAAAGTAAGGTTCCTCAATGGATTCATGTGCAACAGGGAGGTCTTGAGTTGCTACATGGAGCTATTTTATGTAGTTATGGGGTTAAACAAGATCCTAGAGCTAAAATAGTATTATCTGCTGGATCTAAATTGAAGATTCTAGATTCAGAGCAAGAAAATAACGCAGAAATTGGAGATCTTGAAGATTCTGTTAATTCAGAAAAAACACCATCTCTTTGGATTGGGAAGAACGCTCAAGCAAAAGTCCCTCTGGTTGATATCCATACTATTTCTATTGATTTAGCATCATTTTCTTCTAAAGCTCAGGAAACCCCTGAGGAAGCTCCACAAGTCATCGTCCCTAAGGGAAGTTGTGTCCACTCGGGAGAGTTAAGTTTGGAGTTGGTTAATACAACAGGAAAAGGTTATGAGAATCATGCGTTGTTAAAAAATGATACTCAGGTTTCTCTCATGTCTTTCAAAGAGGAAAATGATGGATCTTTAGAAGATTTGAGTAAGTTGTCTGTTTCGGATTTACGCATTAAAGTTTCTACTCCAGATATTGTAGAAGAAACTTATGGCCATATGGGGGATTGGTCTGAAGCTACAATTCAAGATGGGGCTCTTGTCATTAATTGGCATCCTACTGGATATAAATTAGATCCGCAAAAAGCTGGTTCTTTGGTATTCAATGCATTATGGGAGGAAGAGGCTGTATTGTCTACTCTAAAAAATGCTCGGATTGCCCATAACCTTACCATTCAGAGAATGGAATTTGATTATTCTACAAATGCTTGGGGATTAGCTTTTAGTAGCTTTAGAGAGCTATCTTCAGAGAAGCTTGTTTCTGTTGATGGATATAGAGGCTCTTATATAGGGGCTTCTGCAGGCATTGATACTCAGTTGATGGAAGATTTTGTTTTGGGAATCAGCACGGCTTCCTTCTTCGGGAAAATGCATAGTCAGAATTTTGATGCAGAGATTTCTCGACATGGTTTTGTTGGTTCGGTCTATACAGGCTTCCTAGCTGGGGCCTGGTTCTTCAAGGGGCAGTACAGTCTTGGCGAAACACATAACGATATGACAACTCGTTACGGGGTTTTGGGAGAATCTAATGCTACTTGGAAGTCTCGAGGAGTACTAGCAGATGCTTTAGTTGAATATCGTAGTTTAGTCGGTCCAGCACGACCTAAATTTTATGCTTTGCATTTTAATCCTTATGTCGAGGTATCTTATGCATCTGCGAAGTTCCCTAGTTTTGTAGAACAAGGAGGAGAAGCTCGTGCTTTTGAAGAAACCTCTTTAACAAACATTACCGTTCCCTTTGGTATGAAATTTGAACTATCTTTTACAAAAGGACAGTTTTCAGAGACTAATTCTCTTGGAATAGGTTGTGCATGGGAAATGTATCGGAAAGTCGAAGGAAGATCTGTAGAGCTACTAGAAGCTGGTTTTGATTGGGAAGGATCTCCTATAGATCTCCCTAAACAAGAGCTGAGAGTGGCTTTAGAAAACAATACGGAATGGAGTTCGTATTTTAGTACAGCTCTAGGAGTAACAGCATTTTGTGGAGGATTTTCTTCTATGGATAATAAACTAGGATACGAAGCGAATGCTGGAATGCGTTTGATTTTCTAG SEQ ID NO: 132 - TC0197 fragment protein sequenceNCSDLYAVGSSADHPAYLIPQAGLLLDHIKDIFIGPKDSQDKGQYKLIIGEAGSFQDSNAETLPQKVEHSTLFSVTTPIIVQGIDQQDQVSSQGLVCNFSGDHSEEIFERESFLGIAFLGNGSKDGITLTDIKSSLSGAALYSSDDLIFERIKGDIELSSCSSLERGGACSAQSILIHDCQGLTVKHCAAGVNVEGVSASDHLGFGGGAFSTTSSLSGEKSLYMPAGDIVVATCDGPVCFEGNSAQLANGGAIAASGKVLFVANEKKISFTDNQALSGGAISASSSISFQNCAELVFKSNLAKGVKDKCSLGGGALASLESVVLKDNLGITYEKNQSYSEGGAIFGKDCEIFENRGPVVFRDNTAALGGGAILAQQTVAICGNKSGISFEGSKSSFGGAIACGNFSSENNSSALGSIDISNNLGDISFLRTLCTTSDLGQTDYQGGGALFAENISLSENAGAITFKDNIVKTFASNGKMLGGGAILASGNVLISKNSGEISFVGNARAPQAIPTRSSDELSFGAQLTQTTSGCSGGGALFGKEVAIVQNATVVFEQNRLQCGEQETHGGGGAVYGMESASIIGNSFVRFGNNYAVGNQISGGALLSKKVRLAENTRVDFSRNIATFCGGAVQVSDGSCELINNGYVLFRDNRGQTFGGAISCLKGDVIISGNKDRVEFRDNIVTRPYFEENEEKVETADINSDKQEAEERSLLENIEQSFITATNQTFFLEEEKLPSEAFISAEELSKRRECAGGAIFAKRVYITDNKEPILFSHNFSDVYGGAIFTGSLQETDKQDVVTPEVVISGNDGDVIFSGNAAKHDKHLPDTGGGAICTQNLTISQNNGNVLFLNNFACSGGAVRIEDHGEVLLEAFGGDIIFNGNSSFRAQGSDAIYFAGKDSRIKALNATEGHAIVFQDALVFENIEERKSSGLLVINSQENEGYTGSVRFLGSESKVPQWIHVQQGGLELLHGAILCSYGVKQDPRAKIVLSAGSKLKILDSEQENNAEIGDLEDSVNSEKTPSLWIGKNAQAKVPLVDIHTISIDLASFSSKAQETPEEAPQVIVPKGSCVHSGELSLELVNTTGKGYENHALLKNDTQVSLMSFKEENDGSLEDLSKLSVSDLRIKVSTPDIVEETYGHMGDWSEATIQDGALVINWHPTGYKLDPQKAGSLVFNALWEEEAVLSTLKNARIAHNLTIQRMEFDYSTNAWGLAFSSFRELSSEKLVSVDGYRGSYIGASAGIDTQLMEDFVLGISTASFFGKMHSQNFDAEISRHGFVGSVYTGFLAGAWFFKGQYSLGETHNDMTTRYGVLGESNATWKSRGVLADALVEYRSLVGPARPKFYALHFNPYVEVSYASAKFPSFVEQGGEARAFEETSLTNITVPFGMKFELSFTKGQFSETNSLGIGCAWEMYRKVEGRSVELLEAGFDWEGSPIDLPKQELRVALENNTEWSSYFSTALGVTAFCGGFSSMDNKLGYEANAGMRLIFSEQ ID NO: 133 - TC0261 fragment nucleotide sequenceACTCGAGAAGTCCCTCCTTCGATTCTTTTAAAGCCTATACTAAATCCATACCATATGACCGGGTTATTTTTTCCCAAGGTTAATTTGCTTGGAGACACACATAATCTCACTGATTACCATTTGGATAATCTAAAATGCATTCTGGCTTGCCTACAAAGAACTCCTTATGAAGGAGCTGCTTTCACAGTAACCGATTACTTAGGTTTTTCAGATACACAAAAGGATGGTATTTTTTGTTTTAAAAATCTTACTCCAGAGAGTGGAGGGGTTATTGGTTCCCCAACTCAAAACACTCCTACTATAAAAATTCATAATACAATCGGCCCCGTTCTTTTCGAAAATAATACCTGTCATAGACTGTGGACACAGACCGATCCCGAAAATGAAGGAAACAAAGCACGCGAAGGCGGGGCAATTCATGCTGGGGACGTTTACATAAGCAATAACCAGAACCTTGTCGGATTCATAAAGAACTTTGCTTATGTTCAAGGTGGAGCTATTAGTGCTAATACTTTTGCCTATAAAGAAAATAAATCGAGCTTTCTTTGCCTAAATAACTCTTGTATACAAACTAAGACGGGAGGGAAAGGTGGTGCTATTTACGTTAGTACGAGCTGCTCTTTCGAGAACAATAACAAGGATCTGCTTTTCATCCAAAACTCCGGCTGTGCAGGAGGAGCTATCTTCTCTCCAACCTGTTCTCTAATAGGAAACCAAGGAGATATTGTTTTTTACAGCAACCACGGTTTTAAAAATGTTGATAATGCAACTAACGAATCTGGGGATGGAGGAGCTATTAAAGTAACTACCCGCTTGGACATCACCAATAATGGTAGTCAAATCTTTTTTTCTGATAATATCTCAAGAAATTTTGGAGGAGCTATTCATGCTCCTTGTCTTCATCTTGTTGGTAATGGGCCAACCTATTTTACAAACAATATAGCTAATCACACAGGTGGGGCTATTTATATAACAGGAACAGAAACCTCAAAGATTTCTGCAGATCACCATGCTATTATTTTTGATAATAACATTTCTGCAAACGCCACCAATGCGGACGGATCTAGCAGCAACACTAATCCTCCTCACAGAAATGCGATCACTATGGACAATTCCGCTGGAGGAATAGAACTTGGTGCAGGGAAGAGCCAGAATCTTATTTTCTATGATCCTATTCAAGTGACGAATGCTGGAGTTACCGTAGACTTCAATAAGGATGCCTCCCAAACCGGATGTGTAGTTTTCTCTGGAGCGACTGTCCTTTCTGCAGATATTTCTCAGGCTAATTTGCAAACTAAAACACCTGCAACGCTTACTCTCAGTCACGGTCTTCTGTGTATCGAAGATCGTGCTCAGCTCACAGTGAACAATTTTACACAAACAGGAGGGATTGTAGCCTTAGGAAATGGAGCAGTTTTAAGCAGCTACCAACACAGCACTACAGACGCCACTCAAACTCCCCCTACAACCACCACTACAGATGCTTCCGTAACTCTTAATCACATTGGATTAAATCTCCCCTCTATTCTTAAGGATGGAGCAGAGATGCCTCTATTATGGGTAGAACCTATAAGCACAACTCAAGGTAACACTACAACATATACGTCAGATACCGCGGCTTCCTTCTCATTAAATGGAGCCACACTCTCTCTCATTGATGAAGATGGAAATTCTCCCTATGAAAACACGGACCTCTCTCGTGCATTGTACGCTCAACCTATGCTAGCAATTTCTGAGGCCAGTGATAACCAATTGCAATCCGAAAGCATGGACTTTTCTAAAGTTAATGTTCCTCACTATGGATGGCAAGGACTTTGGACCTGGGGGTGGGCAAAAACTGAAAATCCAACAACAACTCCTCCAGCAACAATTACTGATCCGAAAAAAGCTAATCAGTTTCATAGAACTTTATTATTAACGTGGCTCCCTGCTGGTTATATCCCCAGCCCTAAACATAAAAGCCCTTTAATAGCTAATACCTTGTGGGGGAATATACTTTTTGCAACGGAAAACTTAAAAAATAGCTCAGGGCAAGAACTTCTTGATCGTCCTTTCTGGGGAATTACAGGAGGGGGCTTGGGGATGATGGTCTATCAAGAACCTAGAAAAGACCATCCTGGATTCCACATGCATACCTCCGGATATTCAGCAGGAATGATTACAGGAAACACACATACCTTCTCATTACGATTCAGCCAGTCCTATACAAAACTCAATGAACGTTATGCCAAGAACTATGTGTCTTCTAAAAATTACTCTTGCCAAGGGGAAATGCTTTTGTCCTTACAAGAAGGACTCATGCTGACTAAACTAATTGGTCTCTATAGTTATGGGAATCACAACAGCCACCATTTCTATACCCAAGGAGAAGACCTATCGTCTCAAGGGGAGTTCCATAGTCAGACTTTTGGAGGGGCTGTCTTTTTTGATCTACCTCTGAAACCTTTTGGAAGAACACACATACTTACAGCTCCTTTCTTAGGTGCCATTGGTATGTATTCTAAGCTGTCTAGCTTTACAGAAGTAGGAGCCTATCCAAGAACCTTTATTACAGAAACGCCTTTAATCAATGTCCTGATTCCTATCGGAGTAAAAGGTAGCTTCATGAATGCCACCCATAGACCTCAGGCCTGGACTGTAGAGCTTGCTTACCAACCTGTTCTTTACAGACAAGAACCTAGTATCTCTACCCAATTACTCGCTGGTAAAGGTATGTGGTTTGGGCATGGAAGTCCTGCATCTCGCCACGCTCTAGCTTATAAAATTTCACAGAAAACACAGCTTTTGCGATTTGCAACACTTCAACTCCAGTATCACGGATACTATTCGTCTTCCACTTTCTGTAATTATCTGAATGGAGAGGTATCTTTACGTTTCSEQ ID NO: 134 - TC0261 fragment protein sequenceTREVPPSILLKPILNPYHMTGLFFPKVNLLGDTHNLTDYHLDNLKCILACLQRTPYEGAAFTVTDYLGFSDTQKDGIFCFKNLTPESGGVIGSPTQNTPTIKIHNTIGPVLFENNTCHRLWTQTDPENEGNKAREGGAIHAGDVYISNNQNLVGFIKNFAYVQGGAISANTFAYKENKSSFLCLNNSCIQTKIGGKGGAIYVSTSCSFENNNKDLLFIQNSGCAGGAIFSPTCSLIGNQGDIVFYSNHGFKNVDNATNESGDGGAIKVITRLDITNNGSQIFFSDNISRNFGGAIHAPCLHLVGNGPTYFTNNIANHTGGAIYITGTETSKISADHHAIIFDNNISANATNADGSSSNTNPPHRNAITMDNSAGGIELGAGKSQNLIFYDPIQVTNAGVTVDFNKDASQTGCVVFSGATVLSADISQANLQTKTPATLTLSHGLLCIEDRAQLTVNNFTQTGGIVALGNGAVLSSYQHSTTDATQTPPTTTTTDASVTLNHIGLNLPSILKDGAEMPLLWVEPISTTQGNTTTYTSDTAASFSLNGATLSLIDEDGNSPYENTDLSRALYAQPMLAISEASDNQLQSESMDFSKVNVPHYGWQGLWTWGWAKTENPTTTPPATITDPKKANQFHRTLLLTWLPAGYIPSPKHKSPLIANTLWGNILFATENLKNSSGQELLDRPFWGITGGGLGMMVYQEPRKDHPGFHMHTSGYSAGMITGNTHTFSLRFSQSYTKLNERYAKNYVSSKNYSCQGEMLLSLQEGLMLTKLIGLYSYGNHNSHHFYTQGEDLSSQGEFHSQTFGGAVFFDLPLKPFGRTHILTAPFLGAIGMYSKLSSFTEVGAYPRTFITETPLINVLIPIGVKGSFMNATHRPQAWTVELAYQPVLYRQEPSISTQLLAGKGMWFGHGSPASRHALAYKISQKTQLLRFATLQLQYHGYYSSSTFCNYLNGEVSLRFSEQ ID NO: 135 - CT600 nucleotide sequenceATGAGAAAGACTATTTTTAAAGCGTTTAATTTATTATTCTCCCTTCTTTTTCTTTCTTCATGCTCTTATCCTTGCAGAGATTGGGAATGCCATGGTTGCGACTCCGCAAGACCTCGTAAATCCTCTTTTGGATTCGTACCTTTCTACTCCGATGAAGAAATTCAACAAGCTTTTGTTGAAGATTTTGATTCCAAAGAAGAGCAGCTGTACAAAACGAGCGCACAGAGTACCTCTTTCCGAAATATCACTTTCGCTACAGATAGTTATTCTATTAAAGGAGAGGATAACCTCACGATTCTTGCAAGCTTAGTTCGTCATTTGCATAAATCTCCTAAAGCTACGCTATATATAGAGGGCCATACAGATGAACGTGGAGCTGCAGCTTATAACCTAGCTTTAGGAGCTCGTCGTGCGAATGCTGTAAAACAATACCTCATCAAACAGGGAATCGCTGCAGACCGCTTATTCACTATTTCTTACGGAAAAGAACATCCTGTTCATCCAGGCCATAATGAATTAGCTTGGCAACAAAATCGTCGTACTGAATTTAAGATCCATGCTCGCTAA SEQ ID NO: 136 - CT600 protein sequenceMRKTIFKAFNLLFSLLFLSSCSYPCRDWECHGCDSARPRKSSFGFVPFYSDEEIQQAFVEDFDSKEEQLYKTSAQSTSFRNITFATDSYSIKGEDNLTILASLVRHLHKSPKATLYIEGHTDERGAAAYNLALGARRANAVKQYLIKQGIAADRLFTISYGKEHPVHPGHNELAWQQNRRTEFKIHARSEQ ID NO: 137 - CT600 fragment nucleotide sequenceTGCTCTTATCCTTGCAGAGATTGGGAATGCCATGGTTGCGACTCCGCAAGACCTCGTAAATCCTCTTTTGGATTCGTACCTTTCTACTCCGATGAAGAAATTCAACAAGCTTTTGTTGAAGATTTTGATTCCAAAGAAGAGCAGCTGTACAAAACGAGCGCACAGAGTACCTCTTTCCGAAATATCACTTTCGCTACAGATAGTTATTCTATTAAAGGAGAGGATAACCTCACGATTCTTGCAAGCTTAGTTCGTCATTTGCATAAATCTCCTAAAGCTACGCTATATATAGAGGGCCATACAGATGAACGTGGAGCTGCAGCTTATAACCTAGCTTTAGGAGCTCGTCGTGCGAATGCTGTAAAACAATACCTCATCAAACAGGGAATCGCTGCAGACCGCTTATTCACTATTTCTTACGGAAAAGAACATCCTGTTCATCCAGGCCATAATGAATTAGCTTGGCAACAAAATCGTCGTACTGAATTTAAGATCCATGCTCGCSEQ ID NO: 138 - CT600 fragment protein sequenceCSYPCRDWECHGCDSARPRKSSFGFVPFYSDEEIQQAFVEDFDSKEEQLYKTSAQSTSFRNITFATDSYSIKGEDNLTILASLVRHLHKSPKATLYIEGHTDERGAAAYNLALGARRANAVKQYLIKQGIAADRLFTISYGKEHPVHPGHWELAWQQNRRTEFKIHAR SEQ ID NO: 139 - CT823 nucleotide sequenceATGATGAAAAGATTATTATGTGTGTTGCTATCGACATCAGTTTTCTCTTCGCCAATGCTAGGCTATAGTGCGTCAAAGAAAGATTCTAAGGCTGATATTTGTCTTGCAGTATCCTCAGGAGATCAAGAGGTTTCACAAGAAGATCTGCTCAAAGAAGTATCCCGAGGATTTTCTCGGGTCGCTGCTAAGGCAACGCCTGGAGTTGTATATATAGAAAATTTTCCTAAAACAGGGAACCAGGCTATTGCTTCTCCAGGAAACAAAAGAGGCTTTCAAGAGAACCCTTTTGATTATTTTAATGACGAATTTTTTAATCGATTTTTTGGATTGCCTTCGCATAGAGAGCAGCAGCGTCCGCAGCAGCGTGATGCTGTAAGAGGAACTGGGTTCATTGTTTCTGAAGATGGTTATGTTGTTACTAACCATCATGTAGTCGAGGATGCAGGAAAAATTCATGTTACTCTCCACGACGGACAAAAATACACAGCTAAGATCGTGGGGTTAGATCCAAAAACAGATCTTGCTGTGATCAAAATTCAAGCGGAGAAATTACCATTTTTGACTTTTGGGAATTCTGATCAGCTGCAGATAGGTGACTGGGCTATTGCTATTGGAAATCCTTTTGGATTGCAAGCAACGGTCACTGTCGGGGTCATTAGTGCTAAAGGAAGAAATCAGCTACATATTGTAGATTTCGAAGACTTTATTCAAACAGATGCTGCCATTAATCCTGGGAATTCAGGCGGTCCATTGTTAAACATCAATGGTCAAGTTATCGGGGTTAATACTGCCATTGTCAGTGGTAGCGGGGGATATATTGGAATAGGGTTTGCTATTCCTAGCTTGATGGCTAAACGAGTCATTGATCAATTGATTAGTGATGGGCAGGTAACAAGAGGCTTTTTGGGAGTTACCTTGCAACCGATAGATTCTGAATTGGCTACTTGTTACAAATTGGAAAAAGTGTACGGAGCTTTGGTGACGGATGTTGTTAAAGGTTCTCCAGCAGAAAAAGCAGGGCTGCGCCAAGAAGATGTCATTGTGGCTTACAATGGAAAAGAAGTAGAGTCTTTGAGTGCGTTGCGTAATGCCATTTCCCTAATGATGCCAGGGACTCGTGTTGTTTTAAAAATCGTTCGTGAAGGGAAAACAATCGAGATACCTGTGACGGTTACACAGATCCCAACAGAGGATGGCGTTTCAGCGTTGCAGAAGATGGGAGTCCGTGTTCAGAACATTACTCCAGAAATTTGTAAGAAACTCGGATTGGCAGCAGATACCCGAGGGATTCTGGTAGTTGCTGTGGAGGCAGGCTCGCCTGCAGCTTCTGCAGGCGTCGCTCCTGGACAGCTTATCTTAGCGGTGAATAGGCAGCGAGTCGCTTCCGTTGAAGAGTTAAATCAGGTTTTGAAAAACTCGAAAGGAGAGAATGTTCTCCTTATGGTTTCTCAAGGAGATGTGGTGCGATTCATCGTCTTGAAATCAGACGAGTAG SEQ ID NO: 140 - CT823 protein sequenceMMKRLLCVLLSTSVFSSPMLGYSASKKDSKADICLAVSSGDQEVSQEDLLKEVSRGFSRVAAKATPGVVYIENFPKTGNQAIASPGNKRGFQENPFDYFNDEFFNRFFGLPSHREQQRPQQRDAVRGTGFIVSEDGYVVTNHHVVEDAGKIHVTLHDGQKYTAKIVGLDPKTDLAVIKIQAEKLPFLTFGNSDQLQIGDWAIAIGNPFGLQATVTVGVISAKGRNQLHIVDFEDFIQTDAAINPGNSGGPLLNINGQVIGVNTAIVSGSGGYIGIGFAIPSLMAKRVIDQLISDGQVTRGFLGVTLQPIDSELATCYKLEKVYGALVTDVVKGSPAEKAGLRQEDVIVAYNGKEVESLSALRNAISLMIWGTRVVLKIVREGKTIEIPVTVTQIPTEDGVSALQKMGVRVQNITPEICKKLGLAADTRGILVVAVEAGSPAASAGVAPGQLILAVNRQRVASVEELNQVLKNSKGENVLLMVSQGDVVRFIVLKSDESEQ ID NO: 141 - CT823 fragment nucleotide sequenceTCGCCAATGCTAGGCTATAGTGCGTCAAAGAAAGATTCTAAGGCTGATATTTGTCTTGCAGTATCCTCAGGAGATCAAGAGGTTTCACAAGAAGATCTGCTCAAAGAAGTATCCCGAGGATTTTCTCGGGTCGCTGCTAAGGCAACGCCTGGAGTTGTATATATAGAAAATTTTCCTAAAACAGGGAACCAGGCTATTGCTTCTCCAGGAAACAAAAGAGGCTTTCAAGAGAACCCTTTTGATTATTTTAATGACGAATTTTTTAATCGATTTTTTGGATTGCCTTCGCATAGAGAGCAGCAGCGTCCGCAGCAGCGTGATGCTGTAAGAGGAACTGGGTTCATTGTTTCTGAAGATGGTTATGTTGTTACTAACCATCATGTAGTCGAGGATGCAGGAAAAATTCATGTTACTCTCCACGACGGACAAAAATACACAGCTAAGATCGTGGGGTTAGATCCAAAAACAGATCTTGCTGTGATCAAAATTCAAGCGGAGAAATTACCATTTTTGACTTTTGGGAATTCTGATCAGCTGCAGATAGGTGACTGGGCTATTGCTATTGGAAATCCTTTTGGATTGCAAGCAACGGTCACTGTCGGGGTCATTAGTGCTAAAGGAAGAAATCAGCTACATATTGTAGATTTCGAAGACTTTATTCAAACAGATGCTGCCATTAATCCTGGGAATTCAGGCGGTCCATTGTTAAACATCAATGGTCAAGTTATCGGGGTTAATACTGCCATTGTCAGTGGTAGCGGGGGATATATTGGAATAGGGTTTGCTATTCCTAGCTTGATGGCTAAACGAGTCATTGATCAATTGATTAGTGATGGGCAGGTAACAAGAGGCTTTTTGGGAGTTACCTTGCAACCGATAGATTCTGAATTGGCTACTTGTTACAAATTGGAAAAAGTGTACGGAGCTTTGGTGACGGATGTTGTTAAAGGTTCTCCAGCAGAAAAAGCAGGGCTGCGCCAAGAAGATGTCATTGTGGCTTACAATGGAAAAGAAGTAGAGTCTTTGAGTGCGTTGCGTAATGCCATTTCCCTAATGATGCCAGGGACTCGTGTTGTTTTAAAAATCGTTCGTGAAGGGAAAACAATCGAGATACCTGTGACGGTTACACAGATCCCAACAGAGGATGGCGTTTCAGCGTTGCAGAAGATGGGAGTCCGTGTTCAGAACATTACTCCAGAAATTTGTAAGAAACTCGGATTGGCAGCAGATACCCGAGGGATTCTGGTAGTTGCTGTGGAGGCAGGCTCGCCTGCAGCTTCTGCAGGCGTCGCTCCTGGACAGCTTATCTTAGCGGTGAATAGGCAGCGAGTCGCTTCCGTTGAAGAGTTAAATCAGGTTTTGAAAAACTCGAAAGGAGAGAATGTTCTCCTTATGGTTTCTCAAGGAGATGTGGTGCGATTCATCGTCTTGAAATCAGACGAGSEQ ID NO: 142 - CT823 fragment protein sequenceSPMLGYSASKKDSKADICLAVSSGDQEVSQEDLLKEVSRGFSRVAAKATPGVVYIENFPKTGNQAIASPGNKRGFQENPFDYFNDEFFNRFFGLPSHREQQRPQQRDAVRGTGFIVSEDGYVVTNHHVVEDAGKIHVTLHDGQKYTAKIVGLDPKTDLAVIKIQAEKLPFLTFGNSDQLQIGDWAIAIGNPFGLQATVTVGVISAKGRNQLHIVDFEDFIQTDAAINPGNSGGPLLNINGQVIGVNTAIVSGSGGYIGIGFAIPSLMAKRVIDQLISDGQVTRGFLGVTLQPIDSELATCYKLEKVYGALVTDVVKGSPAEKAGLRQEDVIVAYNGKEVESLSALRNAISLMMPGTRVVLKIVREGKTIEIPVTVTQIPTEDGVSALQKMGVRVQNITPEICKKLGLAADTRGILVVAVEAGSPAASAGVAPGQLILAVNRQRVASVEELNQVLKNSKGENVLLMVSQGDVVRFIVLKSDE SEQ ID NO: 143 - TC0106 nucleotide sequenceATGCTAACTAACTTTACCTTTCGCAACTGTCTTTTGTTTTTCGTCACATTGTCCAGTGTCCCTGTTTTCTCGGCACCCCAACCTCGCGTAACGCTTCCTAGTGGAGCCAATAAAATCGGATCAGAAGCTTGGATAGAGCAAAAAGTCCGTCAATATCCAGAACTTTTGTGGTTAGTTGAACCTTCTCCTGCAGGAACTTCTTTAAACGCTCCTTCGGGGATGATCTTTTCTCCCCTATTGTTCCAAAAGAAAGTCCCTGCTTTTGATATCGCAGTACGCAGTCTGATTCACCTACACCTGCTTATCCAGGGCTCCCGCCAAGCTTATGCTCAGCTTGTCCAGCTGCAGGCTAATGAATCCCCTATGACATTTAAACAGTTCCTTACCCTACATAAGCAGCTCTCCTTATTCCTAAATTCTCCTAAAGAGTTTTATGATTCCGTCAAAATTTTAGAAACTGCTATCATCCTACGCCACTTAGGATGTTCAACAAAAGCTGTTGCCACATTTAAGCCTTATTTTTCAGAAACGCAAAAAGAGGTCTTCTATACAAAAGCTTTGCATGTTCTGCATACTTTCCCAGAATTGAGCCCTTCGTTTGCTAGACTCTCTCCAGAACAAAAAACGCTCTTCTTCTCATTGAGAAAGCTCGCTAATTATGATGAGTTACTTTCCCTGACAAATGCCCCTAGTTTACAACTACTATCTGCTGTACGCTCGCGACGCGCGCTTTTGGCTCTAGACTTGTATCTCTATGCTTTAGATTTTTGTGGAGAACAGGGGATATCCTCTCAGTTTCATATGGACTTTTCTCCTTTACAGTCCATGTTGCAACAATATGCTACGGTTGAAGAAGCCTTCTCCCGCTACTTTACTTACCGAGCTAATCGCCTAGGATTTGCGGGTTCTTCTCGAACTGAAATGGCCTTAGTTAGAATAGCTACTTTAATGAACCTATCCCCTTCAGAAGCTGCTATTTTAACAACAAGCTTTAAGTCTCTTTCCTTGGAAGATGCTGAAAGCTTAGTGAATAGCTTTTATACAAATAAGGGAGACTCTTTAGCTCTTTCTTTACGAGGACTACCAACTCTTATATCTGAACTAACACGCGCTGCGCATGGAAATACGAATGCGGAAGCTCGAGCTCAGCAAATTTACGCCACAACGTTATCATTGGTAGCAAAAAGCTTGAAAGCTCACAAAGAGATGCAAAACAAACAAATTCTTCCCGAAGAAGTCGTTTTAGATTTCTCTGAAACTGCTTCTTCCTGTCAAGGATTGGACATCTTCTCTGAGAACGTTGCTGTTCAAATCCACTTGAATGGATCTGTCAGCATCCATCTATAASEQ ID NO: 144 - TC0106 protein sequenceMLTNFTFRNCLLFFVTLSSVPVFSAPQPRVTLPSGANKIGSEAWIEQKVRQYPELLWLVEPSPAGTSLNAPSGMIFSPLLFQKKVPAFDIAVRSLIHLHLLIQGSRQAYAQLVQLQANESPMTFKQFLTLHKQLSLFLNSPKEFYDSVKILETAIILRHLGCSTKAVATFKPYFSETQKEVFYTKALHVLHTFPELSPSFARLSPEQKTLFFSLRKLANYDELLSLTNAPSLQLLSAVRSRRALLALDLYLYALDFCGEQGISSQFHMDFSPLQSMLQQYATVEEAFSRYFTYRANRLGFAGSSRTEMALVRIATLMNLSPSEAAILTTSFKSLSLEDAESLVNSFYTNKGDSLALSLRGLPTLISELTRAAHGNTNAEARAQQIYATTLSLVAKSLKAHKEMQNKQILPEEVVLDFSETASSCQGLDIFSENVAVQIHLNGSVSIHLSEQ ID NO: 145 - TC0106 fragment nucleotide sequenceTCAGAAGCTTGGATAGAGCAAAAAGTCCGTCAATATCCAGAACTTTTGTGGTTAGTTGAACCTTCTCCTGCAGGAACTTCTTTAAACGCTCCTTCGGGGATGATCTTTTCTCCCCTATTGTTCCAAAAGAAAGTCCCTGCTTTTGATATCGCAGTACGCAGTCTGATTCACCTACACCTGCTTATCCAGGGCTCCCGCCAAGCTTATGCTCAGCTTGTCCAGCTGCAGGCTAATGAATCCCCTATGACATTTAAACAGTTCCTTACCCTACATAAGCAGCTCTCCTTATTCCTAAATTCTCCTAAAGAGTTTTATGATTCCGTCAAAATTTTAGAAACTGCTATCATCCTACGCCACTTAGGATGTTCAACAAAAGCTGTTGCCACATTTAAGCCTTATTTTTCAGAAACGCAAAAAGAGGTCTTCTATACAAAAGCTTTGCATGTTCTGCATACTTTCCCAGAATTGAGCCCTTCGTTTGCTAGACTCTCTCCAGAACAAAAAACGCTCTTCTTCTCATTGAGAAAGCTCGCTAATTATGATGAGTTACTTTCCCTGACAAATGCCCCTAGTTTACAACTACTATCTGCTGTACGCTCGCGACGCGCGCTTTTGGCTCTAGACTTGTATCTCTATGCTTTAGATTTTTGTGGAGAACAGGGGATATCCTCTCAGTTTCATATGGACTTTTCTCCTTTACAGTCCATGTTGCAACAATATGCTACGGTTGAAGAAGCCTTCTCCCGCTACTTTACTTACCGAGCTAATCGCCTAGGATTTGCGGGTTCTTCTCGAACTGAAATGGCCTTAGTTAGAATAGCTACTTTAATGAACCTATCCCCTTCAGAAGCTGCTATTTTAACAACAAGCTTTAAGTCTCTTTCCTTGGAAGATGCTGAAAGCTTAGTGAATAGCTTTTATACAAATAAGGGAGACTCTTTAGCTCTTTCTTTACGAGGACTACCAACTCTTATATCTGAACTAACACGCGCTGCGCATGGAAATACGAATGCGGAAGCTCGAGCTCAGCAAATTTACGCCACAACGTTATCATTGGTAGCAAAAAGCTTGAAAGCTCACAAAGAGATGCAAAACAAACAAATTCTTCCCGAAGAAGTCGTTTTAGATTTCTCTGAAACTGCTTCTTCCTGTCAAGGATTGGACATCTTCTCTGAGAACGTTGCTGTTCAAATCCACTTGAATGGATCTGTCAGCATCCATCTASEQ ID NO: 146 - TC0106 fragment protein sequenceSEAWIEQKVRQYPELLWLVEPSPAGTSLNAPSGMIFSPLLFQKKVPAFDIAVRSLIHLHLLIQGSRQAYAQLVQLQANESPMTFKQFLTLHKQLSLFLNSPKEFYDSVKILETAIILRHLGCSTKAVATFKPYFSETQKEVFYTKALHVLHTFPELSPSFARLSPEQKTLFFSLRKLANYDELLSLTNAPSLQLLSAVRSRRALLALDLYLYALDFCGEQGISSQFHMDFSPLQSMLQQYATVEEAFSRYFTYRANRLGFAGSSRTEMALVRIATLMNLSPSEAAILTTSFKSLSLEDAESLVNSFYTNKGDSLALSLRGLPTLISELTRAAHGNTNAEARAQQIYATTLSLVAKSLKAHKEMQNKQILPEEVVLDFSETASSCQGLDIFSENVAVQIHLNGSVSIHL SEQ ID NO: 147 - TC0431 nucleotide sequenceATGCCCCACTCTCCTTTTTTATATGTTGTTCAACCGCATTCTGTTTTTAATCCTAGATTGGGAGAGCGGCACCCTATTACTTTAGATTTCATCAAAGAAAAGAATCGATTAGCTGATTTTATTGAAAACCTACCTTTAGAAATTTTTGGAGCCCCTTCTTTCTTGGAAAATGCTTCTTTAGAAGCCTCTTATGTCTTGTCTAGGGAATCCACAAAAGATGGCACTCTTTTTACCGTTCTAGAACCCAAACTATCTGCCTGCGTAGCTACTTGCCTTGTGGATTCTTCTATTCCTATGGAGCCCGATAACGAGCTCTTAGAAGAAATTAAACACACTTTGTTGAAAAGCTCTTGTGATGGCGTACAATATCGTGTAACCCGAGAGACTCTCCAAAACAAAGATGAAGCCCCCAGAGTCTCTTTAGTTGCTGATGATATCGAACTTATCCGCAATGTAGATTTTTTAGGACGTTCCGTTGATATTGTAAAATTGGATCCCTTGAATATTCCTAATACCGTAAGCGAGGAGAATGCTCTCGATTACTCTTTCACAAGGGAAACCGCCAAACTTAGCCCTGACGGACGAGTTGGCATCCCTCAAGGGACAAAAATTTTGCCAGCTCCCTCTCTTGAAGTTGAAATTAGCACCTCTATTTTTGAGGAAACCTCTTCTTTTGAACAAAACTTTTCTTCCTCTATTACTTTTTGTGTACCACCTCTTACCTCTTTTTCTCCTTTGCAAGAACCTCCTCTAGTGGGAGCTGGACAGCAGGAAATTCTTGTGACTAAAAAGCACTTATTCCCTAGCTATACCCCTAAACTTATTGATATTGTCAAACGACACAAAAGAGACGCAAAGATTCTAGTAAACAAGATCCAGTTCGAGAAACTATGGAGAAGTCATGCCAAAAGTCAAATCTTAAAAGAAGGCTCTGTTCGCTTGGATTTACAAGGATTTACAGGGGAGCTGTTTAACTACCAACTTCAAGTAGGATCTCATACAATTGCAGCCGTGTTAATTGATCCGGAAATTGCTAACGTCAAATCCCTCCCCGAACAAACTTACGCTGTAAGAAAAATTAAATCAGGGTTCCAATGTAGTTTGGATGACCAACACATTTATCAAGTCGCAGTAAAAAAACATCTTTCTCTGTCTTCACAACCTCCGAAGATATCTCCGTTATCTCAATCCGAAAGCTCCGATTTAAGTCTCTTTGAAGCAGCAGCGTTTTCAGCAAGCCTAACTTACGAGTTCGTAAAGAAAAATACATATCATGCTAAGAATACTGTAACTTGCTCCACGGTATCGCACTCTCTGTATATTCTCAAAGAAGATGACGGGGCTAATGCTGCAGAAAAACGCTTAGACAACAGTTTCCGAAACTGGGTCGAAAATAAGTTGAACGCAAATTCTCCAGATTCTTGTACTGCATTTATTCAAAAATTCGGCACACATTACATCACATCGGCAACTTTTGGAGGATCTGGGTTCCAAGTTCTTAAATTATCCTTTGAACAGGTAGAAGGCCTCCGTAGTAAGAAGATCTCCCTAGAAGCAGCAGCAGCAAATTCCTTATTAAAAAGCTCTGTGTCAAACAGCACGGAATCTGGCTACTCTACTTACGATTCCTCTTCTTCTTCTCATACAGTATTCCTAGGGGGCACTGTATTACCCTCTGTTCATGATGGACAGTTAGATTTTAAAGATTGGTCTGAAAGTGTCTGTTTAGAACCTGTTCCCATTCACATTTCTTTACTCCCCTTAACAGACTTGCTCACCCCTCTTTATTTTCCTGAAACGGATACAACCGAACTATCTAATAAACGTAATGCTCTCCAACAAGCGGTTCGAGTTTACCTTAAAGACCATCGTTCAGCTAAACAAAGCGAACGCTCCGTATTCACAGCGGGGATCAATAGTCCTTCTTCCTGGTTCACATTAGAATCTGCTAATTCACCTCTTGTTGTGAGTTCTCCTTACATGACGTATTGGTCTACTCTCCCCTATCTCTTCCCCACATTAAAAGAGCGTTCTTCAGCAGCTCCCATCGTTTTTTATTTTTGTGTGGATAATAATGAACACGCCTCCCAAAAAATTTTAAACCAAACATATTGCTTCATAGGTTCTTTACCTATTCGACAAAAGATTTTTGGCAGAGAATTTGCTGAGAATCCTTATTTATCTTTCTATGGAAGGTTTGGAGAAGCTTATTTTGATGGCGGTTATCCAGAACGTTGTGGATGGATTGTTGAAAAGTTAAATACTACTAAAGATCAAATTCTCCGCGATGAGGATGAAGTGCAACTAAAGCATGTTTATAGCGGAGAGTATCTGTCTACAATTCCTATTAAGGATTCCCATTGCACACTCTCGCGTACATGCACCGAATCGAATGCTGTTTTTATTATCAAAAAACCTTCGAGCTATTGASEQ ID NO: 148 - TC0431 protein sequenceMPHSPFLYVVQPHSVFNPRLGERHPITLDFIKEKNRLADFIENLPLEIFGAPSFLENASLEASYVLSRESTKDGTLFTVLEPKLSACVATCLVDSSIPMEPDNELLEEIKHTLLKSSCDGVQYRVTRETLQNKDEAPRVSLVADDIELIRNVDFLGRSVDIVKLDPLNIPNTVSEENALDYSFTRETAKLSPDGRVGIPQGTKILPAPSLEVEISTSIFEETSSFEQNFSSSITFCVPPLTSFSPLQEPPLVGAGQQEILVTKKHLFPSYTPKLIDIVKRHKRDAKILVNKIQFEKLIRSHAKSQILKEGSVRLDLQGFTGELFNYQLQVGSHTIAAVLIDPEIANVKSLPEQTYAVRKIKSGFQCSLDDRHIYQVAVKKHLSLSSQPPKISPLSQSESSDLSLFEAAAFSASLTYEFVKKNTYHAKNIVTCSTVSHSLYILKEDDGANAAEKRLDNSFRNWVENKLNANSPDSCTAFIQKFGTHYITSATFGGSGFQVLKLSFEQVEGLRSKKISLEAAAANSLLKSSVSNSTESGYSTYDSSSSSHTVFLGGTVLPSVHDGQLDFKDWSESVCLEPVPIHISLLPLTDLLTPLYFPETDTTELSNKRNALQQAVRVYLKDHRSAKQSERSVFTAGINSPSSWFTLESANSPLVVSSPYMTYWSTLPYLFPTLKERSSAAPIVFYFCVDNNEHASQKILNQTYCFIGSLPIRQKIFGREFAENPYLSFYGRFGEAYFDGGYPERCGWIVEKLNTTKDQILRDEDEVQLKHVYSGEYLSTIPIKDSHCTLSRTCTESNAVFIIKKPSSYSEQ ID NO: 149 - TC0431 fragment nucleotide sequenceCCCCACTCTCCTTTTTTATATGTTGTTCAACCGCATTCTGTTTTTAATCCTAGATTGGGAGAGCGGCACCCTATTACTTTAGATTTCATCAAAGAAAAGAATCGATTAGCTGATTTTATTGAAAACCTACCTTTAGAAATTTTTGGAGCCCCTTCTTTCTTGGAAAATGCTTCTTTAGAAGCCTCTTATGTCTTGTCTAGGGAATCCACAAAAGATGGCACTCTTTTTACCGTTCTAGAACCCAAACTATCTGCCTGCGTAGCTACTTGCCTTGTGGATTCTTCTATTCCTATGGAGCCCGATAACGAGCTCTTAGAAGAAATTAAACACACTTTGTTGAAAAGCTCTTGTGATGGCGTACAATATCGTGTAACCCGAGAGACTCTCCAAAACAAAGATGAAGCCCCCAGAGTCTCTTTAGTTGCTGATGATATCGAACTTATCCGCAATGTAGATTTTTTAGGACGTTCCGTTGATATTGTAAAATTGGATCCCTTGAATATTCCTAATACCGTAAGCGAGGAGAATGCTCTCGATTACTCTTTCACAAGGGAAACCGCCAAACTTAGCCCTGACGGACGAGTTGGCATCCCTCAAGGGACAAAAATTTTGCCAGCTCCCTCTCTTGAAGTTGAAATTAGCACCTCTATTTTTGAGGAAACCTCTTCTTTTGAACAAAACTTTTCTTCCTCTATTACTTTTTGTGTACCACCTCTTACCTCTTTTTCTCCTTTGCAAGAACCTCCTCTAGTGGGAGCTGGACAGCAGGAAATTCTTGTGACTAAAAAGCACTTATTCCCTAGCTATACCCCTAAACTTATTGATATTGTCAAACGACACAAAAGAGACGCAAAGATTCTAGTAAACAAGATCCAGTTCGAGAAACTATGGAGAAGTCATGCCAAAAGTCAAATCTTAAAAGAAGGCTCTGTTCGCTTGGATTTACAAGGATTTACAGGGGAGCTGTTTAACTACCAACTTCAAGTAGGATCTCATACAATTGCAGCCGTGTTAATTGATCCGGAAATTGCTAACGTCAAATCCCTCCCCGAACAAACTTACGCTGTAAGAAAAATTAAATCAGGGTTCCAATGTAGTTTGGATGACCAACACATTTATCAAGTCGCAGTAAAAAAACATCTTTCTCTGTCTTCACAACCTCCGAAGATATCTCCGTTATCTCAATCCGAAAGCTCCGATTTAAGTCTCTTTGAAGCAGCAGCGTTTTCAGCAAGCCTAACTTACGAGTTCGTAAAGAAAAATACATATCATGCTAAGAATACTGTAACTTGCTCCACGGTATCGCACTCTCTGTATATTCTCAAAGAAGATGACGGGGCTAATGCTGCAGAAAAACGCTTAGACAACAGTTTCCGAAACTGGGTCGAAAATAAGTTGAACGCAAATTCTCCAGATTCTTGTACTGCATTTATTCAAAAATTCGGCACACATTACATCACATCGGCAACTTTTGGAGGATCTGGGTTCCAAGTTCTTAAATTATCCTTTGAACAGGTAGAAGGCCTCCGTAGTAAGAAGATCTCCCTAGAAGCAGCAGCAGCAAATTCCTTATTAAAAAGCTCTGTGTCAAACAGCACGGAATCTGGCTACTCTACTTACGATTCCTCTTCTTCTTCTCATACAGTATTCCTAGGGGGCACTGTATTACCCTCTGTTCATGATGGACAGTTAGATTTTAAAGATTGGTCTGAAAGTGTCTGTTTAGAACCTGTTCCCATTCACATTTCTTTACTCCCCTTAACAGACTTGCTCACCCCTCTTTATTTTCCTGAAACGGATACAACCGAACTATCTAATAAACGTAATGCTCTCCAACAAGCGGTTCGAGTTTACCTTAAAGACCATCGTTCAGCTAAACAAAGCGAACGCTCCGTATTCACAGCGGGGATCAATAGTCCTTCTTCCTGGTTCACATTAGAATCTGCTAATTCACCTCTTGTTGTGAGTTCTCCTTACATGACGTATTGGTCTACTCTCCCCTATCTCTTCCCCACATTAAAAGAGCGTTCTTCAGCAGCTCCCATCGTTTTTTATTTTTGTGTGGATAATAATGAACACGCCTCCCAAAAAATTTTAAACCAAACATATTGCTTCATAGGTTCTTTACCTATTCGACAAAAGATTTTTGGCAGAGAATTTGCTGAGAATCCTTATTTATCTTTCTATGGAAGGTTTGGAGAAGCTTATTTTGATGGCGGTTATCCAGAACGTTGTGGATGGATTGTTGAAAAGTTAAATACTACTAAAGATCAAATTCTCCGCGATGAGGATGAAGTGCAACTAAAGCATGTTTATAGCGGAGAGTATCTGTCTACAATTCCTATTAAGGATTCCCATTGCACACTCTCGCGTACATGCACCGAATCGAATGCTGTTTTTATTATCAAAAAACCTTCGAGCTATSEQ ID NO: 150 - TC0431 fragment protein sequencePHSPFLYVVQPHSVFNPRLGERHPITLDFIKEKNRLADFIENLPLEIFGAPSFLENASLEASYVLSRESTKDGTLFTVLEPKLSACVATCLVDSSIPMEPDNELLEEIKHTLLKSSCDGVQYRVTRETLQNKDEAPRVSLVADDIELIRNVDFLGRSVDIVKLDPLNIPNTVSEENALDYSFTRETAKLSPDGRVGIPQGTKILPAPSLEVEISTSIFEETSSFEQNFSSSITFCVPPLTSFSPLQEPPLVGAGQQEILVIKKHLFPSYTPKLIDIVKRHKRDAKILVNKIQFEKLWRSHAKSQILKEGSVRLDLQGFTGELFNYQLQVGSHTIAAVLIDPEIANVKSLPEQTYAVRKIKSGFQCSLDDQHIYQVAVKKHLSLSSQPPKISPLSQSESSDLSLFEAAAFSASLTYEFVKKNTYHAKNTVTCSTVSHSLYILKEDDGANAAEKRLDNSFRNWVENKLNANSPDSCTAFIQKFGTHYITSATFGGSGFQVLKLSFEQVEGLRSKKISLEAAAANSLLKSSVSNSTESGYSTYDSSSSSHTVFLGGTVLPSVHDGQLDFKDWSESVCLEPVPIHISLLPLTDLLTPLYFPETDTTELSNKRNALQQAVRVYLKDHRSAKQSERSVFTAGINSPSSWFTLESANSPLVVSSPYMTYWSTLPYLFPTLKERSSAAPIVFYFCVDNNEHASQKILNQTYCFIGSLPIRQKIFGREFAENPYLSFYGRFGEAYFDGGYPERCGWIVEKLNTTKDQILRDEDEVQLKHVYSGEYLSTIPIKDSHCTLSRTCTESNAVFIIKKPSSYSEQ ID NO: 151 - TC0210 nucleotide sequenceATGATGAAAAGATTATTATGTGTGTTGCTATCGACATCAGTTTTCTCTTCGCCCATGTTGGGCTATAGTGCGCCAAAGAAAGATTCCAGTACTGGCATTTGTCTTGCAGCATCTCAAAGTGATCGGGAACTTTCCCAAGAAGATTTGCTAAAAGAAGTGTCTAGAGGATTTTCCAAAGTCGCTGCTCAGGCAACTCCAGGAGTTGTGTATATAGAAAATTTTCCTAAAACTGGGAGTCAAGCTATTGCTTCTCCTGGGAATAAAAGGGGTTTTCAAGAGAATCCCTTTGATTATTTCAATGATGAGTTTTTCAATCGATTTTTTGGTTTACCCTCGCATAGAGAGCAGCCTCGTCCCCAACAGCGTGATGCTGTAAGAGGAACAGGTTTTATTGTGTCAGAAGATGGGTACGTTGTGACCAACCATCACGTAGTGGAAGATGCGGGGAAAATTCATGTTACTTTACACGATGGACAAAAATACACCGCAAAAATCATAGGATTAGATCCTAAAACGGATCTCGCTGTGATTAAGATCCAAGCAAAAAATCTCCCTTTTTTAACTTTTGGAAACTCTGATCAGCTTCAGATAGGGGATTGGTCAATAGCCATTGGAAATCCTTTCGGATTACAAGCCACAGTAACCGTTGGCGTGATTAGTGCTAAGGGAAGAAACCAATTACATATTGTTGATTTTGAAGATTTTATTCAGACGGATGCAGCAATTAATCCCGGGAATTCAGGTGGTCCATTATTGAACATTGATGGACAGGTTATTGGAGTGAATACAGCAATCGTTAGCGGTAGCGGGGGATACATTGGAATAGGATTTGCCATTCCTAGCTTAATGGCTAAACGAGTTATTGACCAACTCATTAGCGATGGACAGGTGACGAGAGGATTTTTAGGAGTAACCTTACAGCCTATTGATTCGGAGCTTGCCGCTTGTTACAAATTAGAAAAGGTGTACGGAGCCTTGATTACGGATGTTGTTAAGGGATCTCCTGCAGAAAAAGCAGGTTTGCGCCAGGAAGATGTCATTGTTGCTTACAATGGGAAAGAAGTGGAGTCTTTGAGTGCTTTACGTAATGCGATTTCTTTGATGATGCCAGGGACTCGTGTTGTCTTAAAAGTTGTGCGTGAAGGGAAATTCATTGAAATACCTGTCACTGTTACACAAATTCCTGCGGAGGATGGGGTATCTGCTCTTCAAAAAATGGGAGTTCGGGTACAGAATCTTACTCCAGAGATATGCAAGAAACTAGGATTAGCGTCTGATACTCGAGGGATTTTTGTAGTGTCCGTAGAAGCTGGTTCTCCTGCAGCTTCTGCAGGAGTGGTTCCAGGACAACTTATTCTGGCTGTAAACAGACAGAGAGTTTCTTCTGTTGAAGAATTGAATCAGGTCTTGAAGAATGCAAAAGGAGAGAATGTTCTCCTTATGGTTTCTCAAGGAGAAGTCATTCGATTCGTTGTTTTAAAGTCTGATGAATAG SEQ ID NO: 152 - TC0210 protein sequenceMMKRLLCVLLSTSVFSSPMLGYSAPKKDSSTGICLAASQSDRELSQEDLLKEVSRGFSKVAAQATPGVVYIENFPKTGSQAIASPGNKRGFQENPFDYFNDEFFNRFFGLPSHREQPRPQQRDAVRGTGFIVSEDGYVVTNHHVVEDAGKIHVTLHDGQKYTAKIIGLDPKTDLAVIKIRAKNLPFLTFGNSDQLQIGDWSIAIGNPFGLQATVTVGVISAKGRNQLHIVDFEDFIQTDAAINPGNSGGPLLNIDGQVIGVNTAIVSGSGGYIGIGFAIPSLMAKRVIDQLISDGQVTRGFLGVTLQPIDSELAACYKLEKVYGALITDVVKGSPAEKAGLRQEDVIVAYNGKEVESLSALRNAISLMMPGTRVVLKVVREGKFIEIPVTVTQIPAEDGVSALQKMGVRVQNLTPEICKKLGLASDIRGIFVVSVEAGSPAASAGVVPGQLILAVNRQRVSSVEELNQVLKNAKGENVLLMVSQGEVIRFVVLKSDESEQ ID NO: 153 - TC0210 fragment nucleotide sequenceTCGCCCATGTTGGGCTATAGTGCGCCAAAGAAAGATTCCAGTACTGGCATTTGTCTTGCAGCATCTCAAAGTGATCGGGAACTTTCCCAAGAAGATTTGCTAAAAGAAGTGTCTAGAGGATTTTCCAAAGTCGCTGCTCAGGCAACTCCAGGAGTTGTGTATATAGAAAATTTTCCTAAAACTGGGAGTCAAGCTATTGCTTCTCCTGGGAATAAAAGGGGTTTTCAAGAGAATCCCTTTGATTATTTCAATGATGAGTTTTTCAATCGATTTTTTGGTTTACCCTCGCATAGAGAGCAGCCTCGTCCCCAACAGCGTGATGCTGTAAGAGGAACAGGTTTTATTGTGTCAGAAGATGGGTACGTTGTGACCAACCATCACGTAGTGGAAGATGCGGGGAAAATTCATGTTACTTTACACGATGGACAAAAATACACCGCAAAAATCATAGGATTAGATCCTAAAACGGATCTCGCTGTGATTAAGATCCAAGCAAAAAATCTCCCTTTTTTAACTTTTGGAAACTCTGATCAGCTTCAGATAGGGGATTGGTCAATAGCCATTGGAAATCCTTTCGGATTACAAGCCACAGTAACCGTTGGCGTGATTAGTGCTAAGGGAAGAAACCAATTACATATTGTTGATTTTGAAGATTTTATTCAGACGGATGCAGCAATTAATCCCGGGAATTCAGGTGGTCCATTATTGAACATTGATGGACAGGTTATTGGAGTGAATACAGCAATCGTTAGCGGTAGCGGGGGATACATTGGAATAGGATTTGCCATTCCTAGCTTAATGGCTAAACGAGTTATTGACCAACTCATTAGCGATGGACAGGTGACGAGAGGATTTTTAGGAGTAACCTTACAGCCTATTGATTCGGAGCTTGCCGCTTGTTACAAATTAGAAAAGGTGTACGGAGCCTTGATTACGGATGTTGTTAAGGGATCTCCTGCAGAAAAAGCAGGTTTGCGCCAGGAAGATGTCATTGTTGCTTACAATGGGAAAGAAGTGGAGTCTTTGAGTGCTTTACGTAATGCGATTTCTTTGATGATGCCAGGGACTCGTGTTGTCTTAAAAGTTGTGCGTGAAGGGAAATTCATTGAAATACCTGTCACTGTTACACAAATTCCTGCGGAGGATGGGGTATCTGCTCTTCAAAAAATGGGAGTTCGGGTACAGAATCTTACTCCAGAGATATGCAAGAAACTAGGATTAGCGTCTGATACTCGAGGGATTTTTGTAGTGTCCGTAGAAGCTGGTTCTCCTGCAGCTTCTGCAGGAGTGGTTCCAGGACAACTTATTCTGGCTGTAAACAGACAGAGAGTTTCTTCTGTTGAAGAATTGAATCAGGTCTTGAAGAATGCAAAAGGAGAGAATGTTCTCCTTATGGTTTCTCAAGGAGAAGTCATTCGATTCGTTGTTTTAAAGTCTGATGAASEQ ID NO: 154 - TC0210 fragment protein sequenceSPMLGYSAPKKDSSTGICLAASQSDRELSQEDLLKEVSRGFSKVAAQATPGVVYIENFPKTGSQAIASPGNKRGFQENPFDYFNDEFFNRFFGLPSHREQPRPQQRDAVRGTGFIVSEDGYVVTNHHVVEDAGKIHVTLHDGRKYTAKIIGLDPKTDLAVIKIQAKNLPFLTFGNSDQLQIGDWSIAIGNPFGLQATVTVGVISAKGRNQLHIVDFEDFIQTDAAINPGNSGGPLLNIDGQVIGVNTAIVSGSGGYIGIGFAIPSLMAKRVIDQLISDGQVTRGFLGVTLQPIDSELAACYKLEKVYGALITDVVKGSPAEKAGLRQEDVIVAYNGKEVESLSALRNAISLMMPGTRVVLKVVREGKFIEIPVIVTQIPAEDGVSALQKMGVRVQNLTPEICKKLGLASDTRGIFVVSVEAGSPAASAGVVPGQLILAVNRQRVSSVEELNQVLKNAKGENVLLMVSQGEVIRFVVLKSDE SEQ ID NO: 155 - CT163 nucleotide sequenceATGTTTGTGTCGTTCGATAAATCCCGTTGCAGAGCGGATGTCCCCGATTTTTTTGAAAGGACAGGAAACTTTCTTCTCCATTGTGTGGCAAGAGGGATCAATGTTTTATATCGTGTGAAACAAATCTCTAACTATCCTTCATGCTATTTCTCACATAAAGAGATTTCGTGTTGTCGTCGTATTGCAAACATTGTGATCTGTATTCTCACAGGGCCTCTGATGTTATTGGCCACTGTGTTAGGATTATTAGCGTATAGGTTTTCTTCTACTTACCAGACTTCTTTACAAGAACGCTTTCGTTATAAATATGAACAAAAGCAAGCTTTAGATGAATACCGTGATAGGGAAGAAAAAGTCATTACGCTTCAGAAGTTTTGTAGAGGATTTCTAGTTAGAAATCATTTGCTCAACCAAGAAACTTTAACAACGTGTAAGCAATGGGGGCAAAAACTATTAGAAGGAGAAAAATTCCCAAGGGTCCCAGAAGGACGGTCTCTTGTATATATTTCAAAACAGTTTCCTTCTTTAGTAGCAAAACACGTTGGGGCTCAAGATGCCAGGTCTCGTTGGCATCATATTTTTTCTATGCGCAAAGCGCTTGCTTATTTAGATATTAAGCGCATACGAGCACCACGCGCTAGAGTTTATCAAAACTTTATATTCGAAGAAAAACTTCCTGTTTCACGAATTTCTGTAGATTCAATGTGTCTCTATAAAGAAAATCCACAAGCTTTCGATGAGGCGATCAAAGAACTCTTATTTCTATTTAAAGAAGTGCATTTCAGGGATTTTGTTGTAGAAACAGAGTCTCCAACAGACGATTTCCCCTTAGCCGTGAAAGTACACAACTATTGGGTATGCCCACGATACGATAATTTACCTTTATTTATTCAAGAAGGAAAAGATGGCTCTCCAGAAGGGCGTATAGGACTGGTCGATCTAGAAACTTTTTCTTGGTCTCCACATCCATACCCCGTAGAAGAACTAGCTGTGATGTTTCCTATGCATAAAGAGCTTCTTATGACAGAGGCGAAAAAACTACAAATCCCTTTCTCTACAAAGGAGGTCGAGCGCTCTGTAGAGAAAGGGCTTGCTTTTTTTGAACATATGCTAGGGCATCAAGATTTTTGTTCCCAAAAAAGCGTAACGCCATTGCGTAATTGTGCCCCTTATATTCATCTAGAAGTATGGAGATTCTCACTGAAAATTTTTGATATTTTAAAAGCTGCTATTCAACTAAATGGAGCACTCAATGTTCTGTTATCTCCAGATATTCGAGAGCGGTTGAGTGCTATTTCGGATAAGCAATGGTTGGCTATTAGCTCCCAGGTTACGTCATCGTTACTCGAGCAAGTTTCTACAAACATCTATCAGTCTCATACTGAAGAGGCTAAACGAGTAAATTCTTCAGGGACTTTTATCATGTGTCGATCTCCTATCTTCCGGAAAAGCATCTTCATTAAAAATCTCCCACAATTCTTAAACAAGAAATTGCAGTTGCTTCCAGAGGAGAAAGCAATCAGCGAGGCGCTTGCTTCTCTATGTTTACGTGCAGTAATGGAAGAGCTAGTAGCAACAGGAAATATTTATTCTTATGATTCTATGGATGATTTTTTTGAAGGGCAGTATTGTCGCATTCGTTATTAG SEQ ID NO: 156 - CT163 protein sequenceMFVSFDKSRCRADVPDFFERTGNFLLHCVARGINVLYRVKQISNYPSCYFSHKEISCCRRIANIVICILTGPLMLLATVLGLLAYRFSSTYQTSLQERFRYKYEQKQALDEYRDREEKVITLQKFCRGFLVRNHLLNQETLITCKQWGQKLLEGEKFPRVPEGRSLVYISKQFPSLVAKHVGAQDARSRWHHIFSMRKALAYLDIKRIRAPRARVYQNFIFEEKLPVSRISVDSMCLYKENPQAFDEAIKELLFLFKEVHFRDFVVETESPTDDFPLAVKVHNYWVCPRYDNLPLFIQEGKDGSPEGRIGLVDLETFSWSPHPYPVEELAVMFPMHKELLMTEAKKLQIPFSTKEVERSVEKGLAFFEHMLGHQDFCSQKSVTPLRNCAPYIHLEVWRFSLKIFDILKAAIQLNGALNVLLSPDIRERLSAISDKQWLAISSQVTSSLLEQVSTNIYQSHTEEAKRVNSSGTFIMCRSPIFRKSIFIKNLPQFLNKKLQLLPEEKAISEALASLCLRAVMEELVATGNIYSYDSMDDFFEGQYCRIRY SEQ ID NO: 157 - CT163 fragment nucleotide sequenceTTTGTGTCGTTCGATAAATCCCGTTGCAGAGCGGATGTCCCCGATTTTTTTGAAAGGACAGGAAACTTTCTTCTCCATTGTGTGGCAAGAGGGATCAATGTTTTATATCGTGTGAAACAAATCTCTAACTATCCTTCATGCTATTTCTCACATAAAGAGATTTCGTGTTGTCGTCGTATTGCAAACATTGTGATCTGTATTCTCACAGGGCCTCTGATGTTATTGGCCACTGTGTTAGGATTATTAGCGTATAGGTTTTCTTCTACTTACCAGACTTCTTTACAAGAACGCTTTCGTTATAAATATGAACAAAAGCAAGCTTTAGATGAATACCGTGATAGGGAAGAAAAAGTCATTACGCTTCAGAAGTTTTGTAGAGGATTTCTAGTTAGAAATCATTTGCTCAACCAAGAAACTTTAACAACGTGTAAGCAATGGGGGCAAAAACTATTAGAAGGAGAAAAATTCCCAAGGGTCCCAGAAGGACGGTCTCTTGTATATATTTCAAAACAGTTTCCTTCTTTAGTAGCAAAACACGTTGGGGCTCAAGATGCCAGGTCTCGTTGGCATCATATTTTTTCTATGCGCAAAGCGCTTGCTTATTTAGATATTAAGCGCATACGAGCACCACGCGCTAGAGTTTATCAAAACTTTATATTCGAAGAAAAACTTCCTGTTTCACGAATTTCTGTAGATTCAATGTGTCTCTATAAAGAAAATCCACAAGCTTTCGATGAGGCGATCAAAGAACTCTTATTTCTATTTAAAGAAGTGCATTTCAGGGATTTTGTTGTAGAAACAGAGTCTCCAACAGACGATTTCCCCTTAGCCGTGAAAGTACACAACTATTGGGTATGCCCACGATACGATAATTTACCTTTATTTATTCAAGAAGGAAAAGATGGCTCTCCAGAAGGGCGTATAGGACTGGTCGATCTAGAAACTTTTTCTTGGTCTCCACATCCATACCCCGTAGAAGAACTAGCTGTGATGTTTCCTATGCATAAAGAGCTTCTTATGACAGAGGCGAAAAAACTACAAATCCCTTTCTCTACAAAGGAGGTCGAGCGCTCTGTAGAGAAAGGGCTTGCTTTTTTTGAACATATGCTAGGGCATCAAGATTTTTGTTCCCAAAAAAGCGTAACGCCATTGCGTAATTGTGCCCCTTATATTCATCTAGAAGTATGGAGATTCTCACTGAAAATTTTTGATATTTTAAAAGCTGCTATTCAACTAAATGGAGCACTCAATGTTCTGTTATCTCCAGATATTCGAGAGCGGTTGAGTGCTATTTCGGATAAGCAATGGTTGGCTATTAGCTCCCAGGTTACGTCATCGTTACTCGAGCAAGTTTCTACAAACATCTATCAGTCTCATACTGAAGAGGCTAAACGAGTAAATTCTTCAGGGACTTTTATCATGTGTCGATCTCCTATCTTCCGGAAAAGCATCTTCATTAAAAATCTCCCACAATTCTTAAACAAGAAATTGCAGTTGCTTCCAGAGGAGAAAGCAATCAGCGAGGCGCTTGCTTCTCTATGTTTACGTGCAGTAATGGAAGAGCTAGTAGCAACAGGAAATATTTATTCTTATGATTCTATGGATGATTTTTTTGAAGGGCAGTATTGTCGCATTCGTTATSEQ ID NO: 158 - CT163 fragment protein sequenceFVSFDKSRCRADVPDFFERTGNFLLHCVARGINVLYRVKQISNYPSCYFSHKEISCCRRIANIVICILTGPLMLLATVLGLLAYRFSSTYQTSLQERFRYKYEQKQALDEYRDREEKVITLQKFCRGFLVRNHLLNQETLTICKQWGQKLLEGEKFPRVPEGRSLVYISKQFPSLVAKHVGAQDARSRWHHIFSMRKALAYLDIKRIRAPRARVYQNFIFEEKLPVSRISVDSMCLYKENPQAFDEAIKELLFLFKEVHFRDFVVETESPTDDFPLAVKVHNYWVCPRYDNLPLFIQEGKDGSPEGRIGLVDLETFSWSPHPYPVEELAVMFPNHKELLMTEAKKLQIPFSTKEVERSVEKGLAFFEHMLGHQDFCSQKSVTPLRNCAPYIHLEVWRFSLKIFDILKAAIQLNGALNVLLSPDIRERLSAISDKQWLAISSQVTSSLLEQVSTNIYQSHTEEAKRVNSSGTFIMCRSPIFRKSIFIKNLPQFLNKKLQLLPEEKAISEALASLCLRAVMEELVATGNIYSYDSMDDFFEGQYCRIRY SEQ ID NO: 159 - CT214 nucleotide sequenceATGCGAACAGACTCTCTTTTCAATCCTCCCGACTCTACTAGAGGAGTTTTTCAGTTTTTAGAGACTCAGTGTGATCGAGCCGTGGCTCGGTCCAGACAAAGCCAATTTATAGGGTTAGTCTCTGCTGTAGCAGCTGCAGCATTATTATTGTTGCTTGTGGTCGCTCTATCTGTTCCAGGATTCCCAGTTGCAGCTTCAATTGTTGTAGGGGTTCTCTTTGCTTTATCGATCGTAGCATTAACAGCTTCGTTTTTGGTATATATAGCTAATGCTAAGCTTGTTGCAATAAGAATTAAATTCTTGAGTAGTGGTCTGCAAGATCACTTTTCGGAGTCATCTATTTTAGGGACTCTCCGTAAAGGACGTGGTGCTAGTATTCCGCTTATTTCCGGACAAGCAGATGATCCTCTCCCTAATCGGATTGGGATCAAAAAAAGCACTGAAATGCGTGTTCTTCAAAAAGGAATTGGGACAGATTATAAAAAATATAAGCAGCATCTTGATAGAGTGAATAATGATTTCACTTTTGTCTGTGAGGGGATTAGCGCTTTAATTCCTACAGAAAAAGATGCTCCATTCCCTATAGAACCTTCTCATTTAGCAGGTGTTTTTTTAGTATCATTTTCACCAGACAAGAATCCGATTCTAAAGATTACGCGTCATGCTGAGAAGATGTTACAGCCTCCTCAAGGCGGATTCCCTAACGGGCTGGTTTGGTTGTGTGGAGCTCTTTCTGATCCTAAGAAATTTGCAGCTCCCTTTCTATCTTTGATTGAGAAGACTCACCAAGGGATTTTGGTGAGTAAAGACTTGAAAGACAATAAGGAAAGAAAGCTAGCTTTAGAGGCTTCCCTTCTTTCATTGAATATTTTCTTTTCCGGTTGGTGTTTGGGGAATCCGGAGTACAATCAGTATATCACAACTGCTGTAGCTGAGAAATATAGGGATGTCTCTGTAAGAAATTGTATTTATGATTTCCTGGATACAGGGAATGTGATTTCAGCTCTTGCTTTAGCAAGTAGTTATTCACAAGATTCCGCTTGGGCTGCAGGGTTGCAGAAAGTTTTACGTGAAGAAGATAAAAAGACTAAGAAAAAGTCACGTGAAGAAGTCTCTTGTTTGTATCGTGATATAGATCCAGGCTGTTGTTTAAGAGCCCTTCCTAAGCGATTTGAATCCAAGTCTTCAGGTAGTCAAGGTAGTCCTAAAGAGCAGTTAAGCTCTTTGTTGAAAGCTTTAGACCAGAAAATTCCTTCAGGGATTTTAGGATTGATTGCAAAAGCTTCTTCTGCAGATCTCAAGGCTGATTTTGCAGGTATGCTTGAAGTTATTAAGCAATTACAAGCTTTATTCGATTCTTACCCACCTTTATGCGAAGACAATATTCTCTTGTGGTTAAGCGCTTCTTTAGAACAAGTAGGCTTGCAGAAGAAATTGAGAACCTTTTTACCTTCATCAGAAAAAAAACTCTTAGAAAGAGTTCTCTCTACATTTTTATTAGGTTTGTATACTCGAGGAGTCTTTTCTGTAGGGCAAGTGAATCAGCTAGCTACTATTTGTAATACTCAGGACTCTACAGAATTCTGCCAGAGAGTAAGTGACCTTTCGTTAATTAAACGAGCTCTACCTGCATTATTTGGTTAA SEQ ID NO: 160 - CT214 protein sequenceMRTDSLFNPPDSTRGVFQFLETQCDRAVARSRQSQFIGLVSAVAAAALLLLLVVALSVPGFPVAASIVVGVLFALSIVALTASFLVYIANAKLVAIRIKFLSSGLQDHFSESSILGTLRKGRGASIPLISGQADDPLPNRIGIKKSTEMRVLQKGIGTDYKKYKQHLDRVNNDFTFVCEGISALIPTEKDAPFPIEPSHLAGVFLVSFSPDKNPILKITRHAEKMLQPPQGGFPNGLVWLCGALSDPKKFAAPFLSLIEKTHQGILVSKDLKDNKERKLALEASLLSLNIFFSGWCLGNPEYNQYITTAVAEKYRDVSVRNCIYDFLDTGNVISALALASSYSQDSAWAAGLQKVLREEDKKTKKKSREEVSCLYRDIDPGCCLRALPKRFESKSSGSQGSPKEQLSSLLKALDQKIPSGILGLIAKASSADLKADFAGMLEVIKQLQALFDSYPPLCEDNILLWLSASLEQVGLQKKLRTFLPSSEKKLLERVLSTFLLGLYTRGVFSVGQVNQLATICNTQDSTEFCQRVSDLSLIKRALPALFG SEQ ID NO: 161 - CT214 fragment nucleotide sequenceCGAACAGACTCTCTTTTCAATCCTCCCGACTCTACTAGAGGAGTTTTTCAGTTTTTAGAGACTCAGTGTGATCGAGCCGTGGCTCGGTCCAGACAAAGCCAATTTATAGGGTTAGTCTCTGCTGTAGCAGCTGCAGCATTATTATTGTTGCTTGTGGTCGCTCTATCTGTTCCAGGATTCCCAGTTGCAGCTTCAATTGTTGTAGGGGTTCTCTTTGCTTTATCGATCGTAGCATTAACAGCTTCGTTTTTGGTATATATAGCTAATGCTAAGCTTGTTGCAATAAGAATTAAATTCTTGAGTAGTGGTCTGCAAGATCACTTTTCGGAGTCATCTATTTTAGGGACTCTCCGTAAAGGACGTGGTGCTAGTATTCCGCTTATTTCCGGACAAGCAGATGATCCTCTCCCTAATCCGATTGGGATCAAAAAAAGCACTGAAATGCGTGTTCTTCAAAAAGGAATTGGGACAGATTATAAAAAATATAAGCAGCATCTTGATAGAGTGAATAATGATTTCACTTTTGTCTGTGAGGGGATTAGCGCTTTAATTCCTACAGAAAAAGATGCTCCATTCCCTATAGAACCTTCTCATTTAGCAGGTGTTTTTTTAGTATCATTTTCACCAGACAAGAATCCGATTCTAAAGATTACGCGTCATGCTGAGAAGATGTTACAGCCTCCTCAAGGCGGATTCCCTAACGGGCTGGTTTGGTTGTGTGGAGCTCTTTCTGATCCTAAGAAATTTGCAGCTCCCTTTCTATCTTTGATTGAGAAGACTCACCAAGGGATTTTGGTGAGTAAAGACTTGAAAGACAATAAGGAAAGAAAGCTAGCTTTAGAGGCTTCCCTTCTTTCATTGAATATTTTCTTTTCCGGTTGGTGTTTGGGGAATCCGGAGTACAATCAGTATATCACAACTGCTGTAGCTGAGAAATATAGGGATGTCTCTGTAAGAAATTGTATTTATGATTTCCTGGATACAGGGAATGTGATTTCAGCTCTTGCTTTAGCAAGTAGTTATTCACAAGATTCCGCTTGGGCTGCAGGGTTGCAGAAAGTTTTACGTGAAGAAGATAAAAAGACTAAGAAAAAGTCACGTGAAGAAGTCTCTTGTTTGTATCGTGATATAGATCCAGGCTGTTGTTTAAGAGCCCTTCCTAAGCGATTTGAATCCAAGTCTTCAGGTAGTCAAGGTAGTCCTAAAGAGCAGTTAAGCTCTTTGTTGAAAGCTTTAGACCAGAAAATTCCTTCAGGGATTTTAGGATTGATTGCAAAAGCTTCTTCTGCAGATCTCAAGGCTGATTTTGCAGGTATGCTTGAAGTTATTAAGCAATTACAAGCTTTATTCGATTCTTACCCACCTTTATGCGAAGACAATATTCTCTTGTGGTTAAGCGCTTCTTTAGAACAAGTAGGCTTGCAGAAGAAATTGAGAACCTTTTTACCTTCATCAGAAAAAAAACTCTTAGAAAGAGTTCTCTCTACATTTTTATTAGGTTTGTATACTCGAGGAGTCTTTTCTGTAGGGCAAGTGAATCAGCTAGCTACTATTTGTAATACTCAGGACTCTACAGAATTCTGCCAGAGAGTAAGTGACCTTTCGTTAATTAAACGAGCTCTACCTGCATTATTTGGT SEQ ID NO: 162 - CT214 fragment protein sequenceRTDSLFNPPDSTRGVFQFLETQCDRAVARSRQSQFIGLVSAVAAAALLLLLVVALSVPGFPVAASIVVGVLFALSIVALTASFLVYIANAKLVAIRIKFLSSGLQDHFSESSILGTLRKGRGASIPLISGQADDPLPNRIGIKKSTEMRVLQKGIGTDYKKYKQHLDRVNNDFTFVCEGISALIPTEKDAPFPIEPSHLAGVFLVSFSPDKNPILKITRHAEKMLQPPQGGFPNGLVWLCGALSDPKKFAAPFLSLIEKTHQGILVSKDLKDNKERKLALEASLLSLNIFFSGWCLGNPEYNQYITTAVAEKYRDVSVRNCIYDFLDTGNVISALALASSYSQDSAWAAGLQKVLREEDKKTKKKSREEVSCLYRDIDPGCCLRALPKRFESKSSGSQGSPKEQLSSLLKALDQKIPSGILGLIAKASSADLKADFAGMLEVIKQLQALFDSYPPLCEDNILLWLSASLEQVGLQKKLRTFLPSSEKKLLERVLSTFLLGLYTRGVFSVGQVNQLATICNTQDSTEFCQRVSDLSLIKRALPALFG SEQ ID NO: 163 - CT721 nucleotide sequenceATGGACGGGACAAAAATTCACGAAACACGCTCCTTCTCTTGGTTAAACAACCAACAAGCCATCCCTCCTTCCGAAATGGTGAAGGAGGCTTTTCAACGTTACGCAGACGTATTTTCGTACAGCGCAAATACCTCCATTCTGACTTTACAAGCAGAAGCTGAAGCTTCTGCCCGCAAACTCACAGGGTGTCAGGAGAAGGCTTTTACCTTTCATTTTATTCTTCATTACCCGAATGTCACGGCCATTATCGTGGCCGCTCTTCTGGAAAACCAAAATGCCTTCCAGGGGCGTAATCACCTTCTTGTTCCTTCTTGCGAGCAACAATTTATCATTAATGCTCTCTGCCGTCGGCAAAACTTAGGGACAACCTATGATTGGGTAACCAGCAAAAACGGCCGCGTAAAAGAATCCGATCTAGCAGAAGCTCTTTCCCCGCGGACCTTGCTGTTTTCCATATCTGCTGCGAATGGTATGACAGGATTTCTGGAAGCGATCCCTGAGCTTGCTGCGTTATGTAAAGAACGCGGGGTAATTTTCCACATAGACCTGAGTGATATCTTAGGAAGATGCGCGCTACCCGCAGAACTCTATCAAGCAGATATCCTTACTTTTTCTTCACAGTCTCTTGGTGGGATTGGTCCCTCAGGAGCGATGTTTATTTCTCCCGCTTTAACAAAATATTTTTCCTTATGGCTTCCTAGTAATCCACAAGTCCCTACCTGCCTGAGTTCTCTTGCAGCTTTTTCTCTTGCCTGTCAGGAACGTACAACCGCTTTCTCCTCTCTTGTGCTTTCTGCTATTTCTTCTCGAGCAGCTCTTAAACAGGCTCTTTCCGCTATTCCTCAAGTCGAATTCCTTTTGGAAGACAGTGCCCCTCGTCTCCCTAATGTCGCTGTCTTTGCTATTCCTGGTATCCCTGCAGAGTCCTTAGGATTTTTCCTTTCCCAGAAAAATATTTTTGTAGGGTTAGGCTATGAACGCTTCCAGCCTCTATCGCAGATTTTACAAAGTTCGGGCATCTCTCCCTTCTTATGCCACAGCGCTTTACACGTATCTTTTACTGAACGTACTCCTACTACACACTTCTCTGCATTAGCAACCGCCTTACAAGAAGGGATCTCTCACCTACAACCACTGGTTACTCAATCCTTATGASEQ ID NO: 164 - CT721 protein sequenceMDGTKIHETRSFSWLNNQQAIPPSEMVKEAFQRYADVFSYSANTSILTLQAEAEASARKLTGCQEKAFTFHFILHYPNVTAIIVAALLENQNAFQGRNHLLVPSCEQQFIINALCRRQNLGTTYDWVTSKNGRVKESDLAEALSPRTLLFSISAANGMTGFLEAIPELAALCKERGVIFHIDLSDILGRCALPAELYQADILTFSSQSLGGIGPSGAMFISPALTKYFSLWLPSNPQVPTCLSSLAAFSLACQERTTAFSSLVLSAISSRAALKQALSAIPQVEFLLEDSAPRLPNVAVFAIPGIPAESLGFFLSQKNIFVGLGYERFQPLSQILQSSGISPFLCHSALHVSFTERTPTTHFSALATALQEGISHLQPLVTQSLSEQ ID NO: 165 - CT721 fragment nucleotide sequenceGACGGGACAAAAATTCACGAAACACGCTCCTTCTCTTGGTTAAACAACCAACAAGCCATCCCTCCTTCCGAAATGGTGAAGGAGGCTTTTCAACGTTACGCAGACGTATTTTCGTACAGCGCAAATACCTCCATTCTGACTTTACAAGCAGAAGCTGAAGCTTCTGCCCGCAAACTCACAGGGTGTCAGGAGAAGGCTTTTACCTTTCATTTTATTCTTCATTACCCGAATGTCACGGCCATTATCGTGGCCGCTCTTCTGGAAAACCAAAATGCCTTCCAGGGGCGTAATCACCTTCTTGTTCCTTCTTGCGAGCAACAATTTATCATTAATGCTCTCTGCCGTCGGCAAAACTTAGGGACAACCTATGATTGGGTAACCAGCAAAAACGGCCGCGTAAAAGAATCCGATCTAGCAGAAGCTCTTTCCCCGCGGACCTTGCTGTTTTCCATATCTGCTGCGAATGGTATGACAGGATTTCTGGAAGCGATCCCTGAGCTTGCTGCGTTATGTAAAGAACGCGGGGTAATTTTCCACATAGACCTGAGTGATATCTTAGGAAGATGCGCGCTACCCGCAGAACTCTATCAAGCAGATATCCTTACTTTTTCTTCACAGTCTCTTGGTGGGATTGGTCCCTCAGGAGCGATGTTTATTTCTCCCGCTTTAACAAAATATTTTTCCTTATGGCTTCCTAGTAATCCACAAGTCCCTACCTGCCTGAGTTCTCTTGCAGCTTTTTCTCTTGCCTGTCAGGAACGTACAACCGCTTTCTCCTCTCTTGTGCTTTCTGCTATTTCTTCTCGAGCAGCTCTTAAACAGGCTCTTTCCGCTATTCCTCAAGTCGAATTCCTTTTGGAAGACAGTGCCCCTCGTCTCCCTAATGTCGCTGTCTTTGCTATTCCTGGTATCCCTGCAGAGTCCTTAGGATTTTTCCTTTCCCAGAAAAATATTTTTGTAGGGTTAGGCTATGAACGCTTCCAGCCTCTATCGCAGATTTTACAAAGTTCGGGCATCTCTCCCTTCTTATGCCACAGCGCTTTACACGTATCTTTTACTGAACGTACTCCTACTACACACTTCTCTGCATTAGCAACCGCCTTACAAGAAGGGATCTCTCACCTACAACCACTGGTTACTCAATCCTTASEQ ID NO: 166 - CT721 fragment protein sequenceDGTKIHETRSFSWLNNQQAIPPSEMVKEAFQRYADVFSYSANTSILTLQAEAEASARKLTGCQEKAFTFHFILHYPNVTAIIVAALLENQNAFQGRNHLLVPSCEQQFIINALCRRQNLGTTYDWVISKNGRVKESDLAEALSPRTLLFSISAANGMTGFLEAIPELAALCKERGVIFHIDLSDILGRCALPAELYQADILTFSSQSLGGIGPSGAMFISPALTKYFSLWLPSNPQVPTCLSSLAAFSLACQERTTAFSSLVLSAISSRAALKQALSAIPQVEFLLEDSAPRLPNVAVFAIPGIPAESLGFFLSQKNIFVGLGYERFQPLSQILQSSGISPFLCHSALHVSFTERTPTTHFSALATALQEGISHLQPLVTQSLSEQ ID NO: 167 - CT127 nucleotide sequenceATGCCGCACCAAGTCTTATTGTCTCCTGTTTGCGATCTTTTATCGAATGCTGAAGGTATAGAGACGCAAGTACTGTTTGGAGAAAGGATATGCAACCATAACCATCGACACTATGCCTATTCTCAACTAGTCTTTTCTTCTATATGGAAGCCATACCCTGGCGACTCTCTACAGAATATTCCTCTATTCTCTTCCCAACTGCAGCCTCCTAATGCTGTTGTCTGCTCTCAAGAAGCTTTTTTAGATCCTTGGCATATCCCCTTACCTTTTGCCGCTCCGCTCCACATAGATAACCAAAATCAAGTGTCCCTATCTCCTGCTAGCATAGCATTATTAAATTCCAATTCCAGAAGTAACTATGCAAAAGCTTTCTGCTCTACCAAAGAGATTCGTTTTTTAAATTCTTCATTCTCTCCAAGAGATTTAGTTTCTTTCGCAGAACAATTGATAGATACTCCGTACGTTTGGGGTGGCCGGTGCATTCATAAACAGCTTCCTCGTAATGGTGTAGATTGTTCGGGGTATATTCAACTACTTTACCAAGTCACAGGAAGAAATATCCCTCGCAATGCTAGAGATCAATACAGAGACTGTTCTCCAGTAAAAGATTTCTCGTCTCTACCTATAGGAGGACTTATCTTCCTCAAGAAAGCAAGCACGGGACAAATCAACCATGTTATGATGAAAATCTCGGAGCATGAATTCATTCATGCTGCGGAAAAAATAGGGAAAGTAGAAAAAGTAATCCTAGGAAATAGGGCTTTCTTTAAAGGGAATCTATTCTGCTCATTAGGTGAACCGCCTATAGAAGCTGTTTTTGGCGTTCCTAAAAATAGAAAAGCCTTCTTTTGA SEQ ID NO: 168 - CT127 protein sequenceMPHQVLLSPVCDLLSNAEGIETQVLFGERICNHNHRHYAYSQLVFSSIWKPYPGDSLCMIPLFSSQLQPPNAVVCSQEAFLDPWHIPLPFAAPLHIDNQNQVSLSPASIALLNSNSRSNYAKAFCSTKEIRFLNSSFSPRDLVSFAEQLIDTPYVWGGRCIHKQLPRNGVDCSGYIQLLYQVTGRNIPRNARDQYRDCSPVKDFSSLPIGGLIFLKKASTGQINHVMMKISEHEFIHAAEKIGKVEKVILGNRAFFKGNLFCSLGEPPIEAVFGVPKNRKAFFSEQ ID NO: 169 - CT127 fragment nucleotide sequenceCCGCACCAAGTCTTATTGTCTCCTGTTTGCGATCTTTTATCGAATGCTGAAGGTATAGAGACGCAAGTACTGTTTGGAGAAAGGATATGCAACCATAACCATCGACACTATGCCTATTCTCAACTAGTCTTTTCTTCTATATGGAAGCCATACCCTGGCGACTCTCTACAGAATATTCCTCTATTCTCTTCCCAACTGCAGCCTCCTAATGCTGTTGTCTGCTCTCAAGAAGCTTTTTTAGATCCTTGGCATATCCCCTTACCTTTTGCCGCTCCGCTCCACATAGATAACCAAAATCAAGTGTCCCTATCTCCTGCTAGCATAGCATTATTAAATTCCAATTCCAGAAGTAACTATGCAAAAGCTTTCTGCTCTACCAAAGAGATTCGTTTTTTAAATTCTTCATTCTCTCCAAGAGATTTAGTTTCTTTCGCAGAACAATTGATAGATACTCCGTACGTTTGGGGTGGCCGGTGCATTCATAAACAGCTTCCTCGTAATGGTGTAGATTGTTCGGGGTATATTCAACTACTTTACCAAGTCACAGGAAGAAATATCCCTCGCAATGCTAGAGATCAATACAGAGACTGTTCTCCAGTAAAAGATTTCTCGTCTCTACCTATAGGAGGACTTATCTTCCTCAAGAAAGCAAGCACGGGACAAATCAACCATGTTATGATGAAAATCTCGGAGCATGAATTCATTCATGCTGCGGAAAAAATAGGGAAAGTAGAAAAAGTAATCCTAGGAAATAGGGCTTTCTTTAAAGGGAATCTATTCTGCTCATTAGGTGAACCGCCTATAGAAGCTGTTTTTGGCGTTCCTAAAAATAGAAAAGCCTTCTTTSEQ ID NO: 170 - CT127 fragment protein sequencePHQVLLSPVCDLLSNAEGIETQVLFGERICNHNHRHYAYSQLVFSSINKPYPGDSLQNIPLFSSQLQPPNAVVCSQEAFLDPWHIPLPFAAPLHIDNQNQVSLSPASIALLNSNSRSNYAKAFCSTKEIRFLNSSFSPRDLVSFAEQLIDTPYVWGGRCIHKQLPRNGVDCSGYIQLLYQVTGRNIPRNARDQYRDCSPVKDFSSLPIGGLIFLKKASTGQINHVMMKISEHEFIHAAEKIGKVEKVILGNRAFFKGNLFCSLGEPPIEAVFGVPKNRKAFF

1. An isolated protein comprising an amino acid sequence of any one ofSEQ ID NO: 2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO: 10, SEQID NO: 12, SEQ ID NO: 14, SEQ ID NO: 16, SEQ ID NO: 18, SEQ ID NO:40,SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO: 48, SEQ ID NO:50,SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO: 136 or SEQ ID NO: 140 for use intherapy or diagnosis.
 2. An isolated protein having 50% or greatersequence identity to a protein according to claim
 1. 3. An isolatedprotein comprising a fragment of the amino acid sequence of claim
 1. 4.The protein according to claim 3, wherein the fragment comprises atleast 8 consecutive amino acids of the amino acid sequence of claim 1.5. An antibody which binds to the protein according to claim 1 for usein therapy or diagnosis.
 6. A nucleic acid molecule which encodes theprotein according claim 1 for use in therapy or diagnosis.
 7. Thenucleic acid molecule according to claim 6, comprising the sequence ofany one of SEQ ID NO: 1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ IDNO:9, SEQ ID NO: 11, SEQ ID NO:13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ IDNO:39, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ IDNO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO: 135 or SEQ ID NO:
 139. 8.A nucleic acid molecule comprising of a fragment of the nucleotidesequence of any one of SEQ ID NO: 1, SEQ ID NO:3, SEQ ID NO:5, SEQ IDNO:7, SEQ ID NO:9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ IDNO: 17, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:43 or SEQ ID NO:45, SEQ IDNO:47, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO: 135 or SEQID NO:
 139. 9. A nucleic acid molecule comprising a nucleotide sequencecomplementary to the nucleic acid molecule according to claim
 6. 10. Anucleic acid molecule comprising a nucleotide sequences having 50% orgreater sequence identity to the nucleic acid molecule according toclaim
 6. 11. A nucleic acid molecule which can hybridise to a nucleicacid molecule according to any claim 6 under high stringency conditions.12. A vector comprising a nucleic acid according to claim 6 for use intherapy or diagnosis.
 13. A host cell comprising a nucleic acid orvector according to claim 6 for use in therapy or diagnosis.
 14. Acomposition comprising the according to claim 1 for use in therapy ordiagnosis.
 15. A composition comprising the nucleic acid, according toclaim
 6. 16. A composition comprising the host cell according to claim13 for use as a pharmaceutical.
 17. The composition according to claim14, for use in the treatment, prevention or diagnosis of Chlamydia. 18.The composition according to claim 17, for use in the treatment,prevention or diagnosis of Chlamydia trachomatis.
 19. A The protein,according to claim 1, for raising an immune response in a mammal. 20.The protein of claim 1, for eliciting antibodies that are capable ofneutralising Chlamydia infection.
 21. The protein of claim 19, whereinthe immune response is a CD4+ ThI cell-mediated response.
 22. The use ofa the protein of claim 1, in the manufacture of a medicament for thetreatment or prevention of infection due to Chlamydia bacteria,particularly Chlamydia trachomatis.
 23. A method of treating, preventingor diagnosing Chlamydia in a patient, comprising administering atherapeutically effective amount of the protein of claim
 1. 24. Themethod of claim 23, further comprising administering one or moreadditional Chlamydia antigens or their encoding nucleic acids.
 25. Themethod according to claim 24, wherein the combination comprisesCT279+CT601, CT372+CT443, CT733+CT153, CT456+CT381,CT279+CT153+CT733+CT601, CT279+CT601+CT372+CT443,CT823+CT733+CT043+CT456, CT387+CT812+CT869, CT387+CT812C+CT869 (orvariants thereof).
 26. The method according to claim 24, wherein the oneor more additional Chlamydia antigens or their encoding nucleic acidsare a combined preparation for simultaneous, separate or sequentialadministration.
 27. A method for diagnosing Chlamydia infection,comprising: (a) contacting the antibody of claim 5 with a biologicalsample suspected of being infected with Chlamydia under conditionssuitable for the formation of antibody-antigen complexes; and (b)detecting said complexes, wherein detection of said complex isindicative of Chlamydia infection.